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Pimentel A, Gonçalves-Silva T, Jasmin, Mendez-Otero R. Isolation and characterization of canine umbilical cord mesenchymal/stromal stem cells. In Vitro Cell Dev Biol Anim 2025:10.1007/s11626-025-01023-4. [PMID: 40325278 DOI: 10.1007/s11626-025-01023-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 01/30/2025] [Indexed: 05/07/2025]
Abstract
Mesenchymal stem cells (MSCs) have therapeutic potential due to their immunomodulatory and anti-inflammatory properties. In veterinary medicine, adipose tissue is the most common source of MSCs to treat canine disease, but the collection process is invasive, and the cells are influenced by the age and health conditions of the donor. These problems enhance interest in seeking alternative MSC sources, such as perinatal tissues. In this study, we developed and validated an optimized protocol for isolating canine umbilical cord MSCs for application in veterinary therapies. Umbilical cords obtained from cesarean sections were processed using three different protocols, involving combinations of mechanical and enzymatic tissue dissociation. The cells were cultured and evaluated for membrane receptors by flow cytometry to identify MSCs and assessed for their differentiation capacity. The number of cells obtained did not differ significantly between the combined protocol with trypsin and collagenase (TRIP + COL) and the collagenase protocol (COL). In in vitro culture, the combined TRIP + COL and COL yielded 12 to 14 times more cells, respectively, in the first passage than the explant (EXP) group, within fewer days of culture. Additionally, the cells obtained from these protocols showed a greater capacity for expansion over passages, and cells from both protocols showed fibroblast-like morphology and proliferation capacity up to the sixth passage. The cells obtained from these protocols were characterized by phenotype: CD45-, CD34-, CD14-, HLA-DR-, CD29+, CD44+, and CD90+, consistent with MSC identity. However, CD90 expression in the cells decreased significantly at sixth passage. Regarding differentiation, cells obtained from the COL protocol showed a capacity for commitment to the chondrogenic and osteogenic lineages. In conclusion, the COL and TRIP + COL protocols were more effective than the EXP protocol in terms of both the number and quality of isolated cells. However, due to its less-aggressive enzymatic nature, we considered the COL protocol to be the best method to obtain canine MSCs.
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Affiliation(s)
- Aline Pimentel
- Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro (IBCCF-UFRJ), Av. Carlos Chagas Filho, 373, Rio de Janeiro, RJ 21941-170, Brazil.
| | - Triciana Gonçalves-Silva
- National Center for Structural Biology and Bioimaging, Federal University of Rio de Janeiro (CENABIO-UFRJ), Av. Carlos Chagas Filho, 373, Rio de Janeiro, RJ 21941-170, Brazil
| | - Jasmin
- Duque de Caxias Campus, NUMPEX-Bio, Federal University of Rio de Janeiro, Estrada de Xerém, 27 - Xerém, Duque de Caxias, RJ 25245-390, Brazil
| | - Rosalia Mendez-Otero
- Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro (IBCCF-UFRJ), Av. Carlos Chagas Filho, 373, Rio de Janeiro, RJ 21941-170, Brazil
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Yu Y, Tao Y, Ma J, Li J, Song Z. Targeting the tumor microenvironment with mesenchymal stem cells based delivery approach for efficient delivery of anticancer agents: An updated review. Biochem Pharmacol 2025; 232:116725. [PMID: 39746456 DOI: 10.1016/j.bcp.2024.116725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 11/14/2024] [Accepted: 12/18/2024] [Indexed: 01/04/2025]
Abstract
Drug delivery to cancer cells continues to present a major therapeutic challenge. Mesenchymal stem cells (MSCs) possess an intrinsic ability to migrate specifically to tumor tissues, making them promising candidates for targeted drug delivery. Evidence from preclinical studies indicates that MSCs loaded with therapeutic anti-cancer agents exhibit considerable anti-tumor activity. Moreover, several clinical trials are currently evaluating their effectiveness in cancer patients. The integration of MSCs with synthetic nanoparticles (NPs) enhances their therapeutic potential, particularly through the use of cell membrane-coated NPs, which represent a significant advancement in the field. This review systematically investigates the tumor microenvironment, the sources of MSCs, the tumor homing mechanisms, and the methods of loading and releasing anticancer drugs from MSCs. Furthermore, cutting-edge strategies to improve the efficacy of MSCs based drug delivery systems (DDS) including the innovative use of MSC membrane coated nanoparticles have been discussed. The study concludes with an overview of the therapeutic use of MSCs as drug carriers, including a detailed analysis of the mechanisms by which MSCs deliver therapeutics to cancer cells, enabling targeted drug delivery. It aims to elucidate the current state of this approach, identify key areas for development, and outline potential future directions for advancing MSCs based cancer therapies.
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Affiliation(s)
- Yang Yu
- Department of Emergency and Critical Care, the Second Hospital of Jilin University, Changchun 130000, China
| | - Ying Tao
- Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun 130000, China
| | - Jingru Ma
- Department of Clinical Laboratory, the Second Hospital of Jilin University, Changchun 130000, China
| | - Jian Li
- Department of Emergency and Critical Care, the Second Hospital of Jilin University, Changchun 130000, China
| | - Zhidu Song
- Department of Ophthalmology, the Second Hospital of Jilin University, Changchun 130000, China.
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Shahrezaei A, Sohani M, Nasirinezhad F. Mesenchymal stem cells as a therapeutic strategy to combat oxidative stress-mediated neuropathic pain. BIOIMPACTS : BI 2025; 15:30648. [PMID: 40256229 PMCID: PMC12008502 DOI: 10.34172/bi.30648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 09/22/2024] [Accepted: 09/30/2024] [Indexed: 04/22/2025]
Abstract
Neuropathic pain, a chronic condition resulting from somatosensory system damage, remains a significant clinical challenge due to its complex pathophysiology and inadequate response to traditional therapies. Oxidative stress, characterized by an imbalance between free radicals production and antioxidant defenses, plays a pivotal role in the development and maintenance of neuropathic pain. Mesenchymal stem cells (MSCs) are multipotent stromal cells with the ability to differentiate into various cell types and possess immunomodulatory, anti-inflammatory, and regenerative properties, making them promising candidates for novel pain management strategies. Preclinical studies demonstrate that MSCs can reduce inflammation, scavenge reactive oxygen species (ROS), promote nerve regeneration, and modulate pain signaling pathways. Various administration routes, including intravenous and intrathecal, have been investigated to optimize MSC delivery and efficacy. Additionally, MSC-derived extracellular vesicles (EVs) represent a cell-free alternative with substantial therapeutic potential. Despite encouraging preclinical findings, further research is needed to refine MSC-based therapies, including the exploration of combination treatments and rigorous clinical trials, to translate these promising results into effective clinical applications for neuropathic pain relief. This review explores the therapeutic potential of MSCs in alleviating oxidative stress-mediated neuropathic pain.
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Affiliation(s)
- Aidin Shahrezaei
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Sohani
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Farinaz Nasirinezhad
- Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran
- Center of Experimental and Comparative Study, Iran University of Medical Sciences, Tehran, Iran
- Department of Physiology, Iran University of Medical Sciences, Tehran, Iran
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Ghamrawi A, Basso R, Shakik N, Haddad L, Nasr Z, Harmouch C. Wharton's Jelly Mesenchymal Stem Cells: Shaping the Future of Osteoarthritis Therapy with Advancements in Chitosan-Hyaluronic Acid Scaffolds. Stem Cells Dev 2025; 34:1-16. [PMID: 39605205 DOI: 10.1089/scd.2024.0033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2024] Open
Abstract
This review explores the potential of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) in cartilage regeneration and osteoarthritis treatment. It covers key factors influencing chondrogenesis, including growth factors, cytokines, and hypoxia, focusing on precise timing. The effectiveness of three-dimensional cultures and scaffold-based strategies in chondrogenic differentiation is discussed. Specific biomaterials such as chitosan and hyaluronic acid are highlighted for tissue engineering. The document reviews clinical applications, incorporating evidence from animal research and early trials and molecular and histological assessments of chondrogenic differentiation processes. It addresses challenges and strategies for optimizing MSC-derived chondrocyte therapy, emphasizing the immunomodulatory properties of these cells. The review concludes as a comprehensive road map for future research and clinical applications in regenerative medicine.
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Affiliation(s)
- Ahed Ghamrawi
- Department of Biology, Faculty of Arts and Sciences, University of Balamand, Tripoli, Lebanon
| | - Rasha Basso
- Department of Medical Laboratory Sciences, Faculty of Health Sciences University of Balamand, Beirut, Lebanon
| | - Nour Shakik
- Department of Biology, Faculty of Arts and Sciences, University of Balamand, Tripoli, Lebanon
| | - Lara Haddad
- Department of Medical Laboratory Sciences, Faculty of Health Sciences University of Balamand, Beirut, Lebanon
| | - Zeina Nasr
- Department of Biology, Faculty of Arts and Sciences, University of Balamand, Tripoli, Lebanon
| | - Chaza Harmouch
- Department of Biology, Faculty of Arts and Sciences, University of Balamand, Tripoli, Lebanon
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Sigaut S, Tardivon C, Jacquens A, Bottlaender M, Gervais P, Habert MO, Monsel A, Roquilly A, Boutonnet M, Galanaud D, Cras A, Boucher-Pillet H, Florence AM, Cavalier I, Menasche P, Degos V, Couffignal C. Effects of intravascular administration of mesenchymal stromal cells derived from Wharton's Jelly of the umbilical cord on systemic immunomodulation and neuroinflammation after traumatic brain injury (TRAUMACELL): study protocol for a multicentre randomised controlled trial. BMJ Open 2024; 14:e091441. [PMID: 39740941 PMCID: PMC11749534 DOI: 10.1136/bmjopen-2024-091441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Accepted: 11/25/2024] [Indexed: 01/02/2025] Open
Abstract
INTRODUCTION Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Treatments for TBI patients are limited and none has been shown to provide prolonged and long-term neuroprotective or neurorestorative effects. A growing body of evidence suggests a link between TBI-induced neuro-inflammation and neurodegenerative post-traumatic disorders. Consequently, new therapies triggering immunomodulation and promoting neurological recovery are the subject of major research efforts. We hypothesise that repeated intravenous treatment with mesenchymal stromal cells derived from Wharton's Jelly of the umbilical cord-derived mesenchymal stromal cells ((WJ-UC-MSC) may be associated with a significant decrease of post-TBI neuroinflammation and improvement of neurological status. METHODS AND ANALYSIS The TRAUMACELL trial is a prospective, national multicentre, phase III, superiority, double-arm comparative randomised (1:1) double-blinded clinical trial. Among patients aged between 18-50, with a severe TBI defined by a Glasgow score less than 12 (within the first 48 hours) with brain traumatic lesion on CT Scan and needing intracranial pressure monitoring, with no other significant organ trauma (abbreviated injury scale<2) and unresponsive to verbal commands after 5 days of sedation discontinuation, 68 will be randomly allocated to receive either WJ-UC-MSC solution or placebo, with three intravenous injections 1 week apart. The primary outcome is the [18F]-DPA-714 signal intensity in corpus callosum measured by dynamic positron emission tomography (PET)-MRI at 6 months after the last injection, blinded to the randomisation arm, to evaluate the post-traumatic neuro-inflammation. ETHICS AND DISSEMINATION The TRAUMACELL trial has been approved by an independent ethics committee (CPP SUD EST II) and French Medicines Agency (2023-504415-33-00) for all study centres. Participant recruitment will be starting in September 2024. Results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER NCT06146062, first posted 24 November 2023 PROTOCOL VERSION IDENTIFIER: TRAUMACELL-V.2.0_20240102.
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Affiliation(s)
- Stéphanie Sigaut
- Anesthesiology and Intensive Care, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, Île-de-France, France
- NeuroDiderot, Neuroprotection of the Developing Brain, Université Paris Cité, INSERM, Paris, Île-de-France, France
| | - Coralie Tardivon
- Hôpital Bichat, DMU PRISME, Biostatistics Department and Clinical Trial Units, Assistance Publique-Hôpitaux de Paris, Paris, Île-de-France, France
| | - Alice Jacquens
- NeuroDiderot, Neuroprotection of the Developing Brain, Université Paris Cité, INSERM, Paris, Île-de-France, France
- Department of Neuroanesthesiology and Neurointensive Care, Pitié Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, Île-de-France, France
| | - Michel Bottlaender
- CEA, INSERM, CNRS, BioMaps, Service Hospitalier Frédéric Joliot, Université Paris-Saclay Faculté des Sciences d'Orsay, Orsay, Île-de-France, France
- CEA, Neurospin, UNIACT, Université Paris-Saclay, Gif-sur-Yvette, Île-de-France, France
| | - Philippe Gervais
- CEA, INSERM, CNRS, BioMaps, Service Hospitalier Frédéric Joliot, Paris-Saclay University Faculty of Science Orsay, Orsay, Île-de-France, France
| | - Marie-Odile Habert
- Hôpital Pitié-Salpêtrière, Department of Nuclear Medicine, Assistance Publique-Hopitaux de Paris, Paris, Île-de-France, France
- CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, LIB, Sorbonne University, Paris, Île-de-France, France
| | - Antoine Monsel
- Hôpital Pitié-Salpêtrière, Multidisciplinary Intensive Care Unit, Department of Anaesthesia and Critical Care, Assistance Publique-Hôpitaux de Paris, Paris, Île-de-France, France
- UMRS_959, Immunology-Immunopathology-Immunotherapy (I3), INSERM, Paris, Île-de-France, France
| | - Antoine Roquilly
- SAR, CHU Nantes, Nantes, France
- Center for Research in Transplantation and Translational Immunology, UMR 1064, Université de Nantes, Nantes, Pays de la Loire, France
| | - Mathieu Boutonnet
- Federation of Anaesthesiology, Intensive Care Unit, Burns and Operating Theatre, Hopital d'Instruction des Armees Percy, Clamart, France
| | - Damien Galanaud
- CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, LIB, Sorbonne University, Paris, Île-de-France, France
- Hôpital de la Pitié-Salpêtrière, Neuroradiology Department, Assistance Publique-Hôpitaux de Paris, Paris, Île-de-France, France
| | - Audrey Cras
- Hôpital Saint-Louis, MEARY Center for Cell and Gene Therapy, Assistance Publique-Hôpitaux de Paris, Paris, Île-de-France, France
| | - Hélène Boucher-Pillet
- Hôpital Saint-Louis, MEARY Center for Cell and Gene Therapy, Assistance Publique-Hôpitaux de Paris, Paris, Île-de-France, France
| | - Aline-Marie Florence
- Hôpital Bichat, DMU PRISME, Biostatistics Department and Clinical Trial Units, Assistance Publique-Hôpitaux de Paris, Paris, Île-de-France, France
| | - Ines Cavalier
- Hôpital Bichat, DMU PRISME, Biostatistics Department and Clinical Trial Units, Assistance Publique-Hôpitaux de Paris, Paris, Île-de-France, France
| | - Philippe Menasche
- Cardiovascular Surgery, Hopital Europeen Georges Pompidou, Paris, France
| | - Vincent Degos
- NeuroDiderot, Neuroprotection of the Developing Brain, Université Paris Cité, INSERM, Paris, Île-de-France, France
- Anesthésie et Neuro-Réanimation chirurgicale Babinski, Assistance Publique Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière, Paris, France
| | - Camille Couffignal
- Unité de recherche Clinique, Hôpital Bichat-Claude-Bernard, Paris, Île-de-France, France
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Chai M, Zhang CY, Chen S, Xu DH. Application of autophagy in mesenchymal stem cells. World J Stem Cells 2024; 16:990-1001. [PMID: 39734481 PMCID: PMC11669988 DOI: 10.4252/wjsc.v16.i12.990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 11/05/2024] [Accepted: 12/02/2024] [Indexed: 12/13/2024] Open
Abstract
In this editorial, we have taken an in-depth look at the article published by Wan et al. The study showed that preconditioning mesenchymal stem cells (MSCs) protected them against programmed cell death, and increased their survival rate and therapeutic potential. Autophagy, a type of programmed cell death, is a major intracellular degradation and recycling pathway that is crucial for maintaining cellular homeostasis, self-renewal, and pluripotency. We have explored the relationship between autophagy and MSCs to determine the role of autophagy in the therapeutic applications of MSCs.
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Affiliation(s)
- Min Chai
- Department of Emergency Medicine, The First Hospital of Jilin University, Changchun 130000, Jilin Province, China
| | - Chun-Yan Zhang
- Department of Rehabilitation Medicine, The First Hospital of Jilin University, Changchun 130000, Jilin Province, China
| | - Shuai Chen
- Department of Emergency Surgery, The First Hospital of Jilin University, Changchun 130000, Jilin Province, China
| | - Da-Hai Xu
- Department of Emergency Medicine, The First Hospital of Jilin University, Changchun 130000, Jilin Province, China.
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Liu L, Hao X, Zhang J, Li S, Han S, Qian P, Zhang Y, Yu H, Kang Y, Yin Y, Zhang W, Chen J, Yu Y, Jiang H, Chai J, Yin H, Chai W. The wound healing of deep partial-thickness burn in Bama miniature pigs is accelerated by a higher dose of hUCMSCs. Stem Cell Res Ther 2024; 15:437. [PMID: 39563365 PMCID: PMC11575178 DOI: 10.1186/s13287-024-04063-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 11/11/2024] [Indexed: 11/21/2024] Open
Abstract
BACKGROUND Deep partial-thickness burns have a significant impact on both the physical and mental health of patients. Our previous study demonstrated human Umbilical Cord Mesenchymal stem cells (hUCMSCs) could enhance the healing of severe burns in small animal burn models, such as rats. Furthermore, our team has developed a deep partial-thickness burn model in Bama miniature pigs, which can be utilized for assessing drug efficacy in preclinical trials for wound healing. Therefore, this study further determine the optimal dosage of hUCMSCs in future clinical practice by comparing the efficacy of low-to-high doses of hUCMSCs on deep partial-thickness burn wounds in Bama miniature pigs. MATERIALS AND METHODS The male Bama miniature pigs (N = 8, weight: 23-28 kg and length: 71-75 cm) were used to establish deep partial-thickness burn models, which used a continuous pressure of 1 kg and contact times of 35 s by the invented electronic burn instrument at 100℃ to prepare 10 round burn wounds with diameter of 5 cm according to our previous report. And then, 0 × 10^7, 1 × 10^7, 2 × 10^7, 5 × 10^7 and 1 × 10^8 doses of hUCMSCs were respectively injected into burn wounds of their corresponding groups. After treatment for 7, 14 and 21 days, the burned wound tissues were obtained for histological evaluation, including HE staining for histopathological changes, immunohistochemistry for neutrophil (MPO+) infiltration and microvessel (CD31+) quantity, as well as Masson staining for collagen deposition. The levels of inflammatory factors TNF-α, IL-1β, IL-10 and angiogenesis factors angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), as well as collagen type-I/type-III of the wound tissues were quantified by ELISA. RESULTS All of doses hUCMSCs can significantly increase wound healing rate and shorten healing time of the deep partial-thickness burn pigs in a dose-dependent manner. Furthermore, all of doses hUCMSCs can significantly promote epithelialization and decreased inflammatory reaction of wound, including infiltration of inflammatory cells and levels inflammatory factors. Meanwhile, the amounts of microvessel were increased in all of doses hUCMSCs group than those in the burn group. Furthermore, the collagen structure was disordered and partially necrotized, and ratios of collagen type-I and type-III were significantly decreased in burn group (4:1 in normal skin tissue), and those of all hUCMSCs groups were significantly improved in a dose-dependent manner. In a word, 1 × 10^8 dose of hUCMSCs could regenerate the deep partial-thickness burn wounds most efficaciously compared to other dosages groups and the burn group. CONCLUSION This regenerative cell therapy study using hUCMSCs demonstrates the best efficacy toward a high dose, that is dose of 1 × 10^8 of hUCMSCs was used as a reference therapeutic dose for treating 20 cm2 deep partial-thickness burns wound in future clinical practice.
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Affiliation(s)
- Lingying Liu
- Department of Nutrition, The Fourth Medical Center Affiliated to PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing, 100037, China.
- Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010110, China.
- Hebei North University, Zhangjiakou, Hebei, 075000, China.
| | - Xingxia Hao
- Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010110, China
| | - Jing Zhang
- Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010110, China
| | - Shaozeng Li
- Department of Clinical Laboratory, The Fourth Medical Center Affiliated to PLA General Hospital, Beijing, 100037, China
| | - Shaofang Han
- Department of Nutrition, The Fourth Medical Center Affiliated to PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing, 100037, China
| | - Peipei Qian
- Department of Nutrition, The Fourth Medical Center Affiliated to PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing, 100037, China
| | - Yong Zhang
- Department of Nutrition, The Fourth Medical Center Affiliated to PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing, 100037, China.
| | - Huaqing Yu
- Department of Nutrition, The Fourth Medical Center Affiliated to PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing, 100037, China
| | - Yuxin Kang
- Hebei North University, Zhangjiakou, Hebei, 075000, China
| | - Yue Yin
- Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010110, China
| | - Weiouwen Zhang
- Department of Nutrition, The Fourth Medical Center Affiliated to PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing, 100037, China
| | - Jianmei Chen
- Department of Health Medicine, The Fourth Medical Center of Chinese PLA General Hospital, Beijing, 100037, China
| | - Yang Yu
- Department of Traditional Chinese Medical Science, The Sixth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Hua Jiang
- Department of Endocrinology, The Fourth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jiake Chai
- Senior Department of Burns and Plastic Surgery, The Fourth Medical Center of PLA General Hospital, Beijing, 100037, China
| | - Huinan Yin
- Senior Department of Burns and Plastic Surgery, The Fourth Medical Center of PLA General Hospital, Beijing, 100037, China
| | - Wei Chai
- Senior Department of Orthopedics, The Fourth Medical Center of PLA General Hospital, Beijing, 100037, China
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Carreira M, Pires-Santos M, Correia CR, Nadine S, Mano JF. Liquefied capsules containing nanogrooved microdiscs and umbilical cord-derived cells for bone tissue engineering. OPEN RESEARCH EUROPE 2024; 4:94. [PMID: 39279819 PMCID: PMC11393531 DOI: 10.12688/openreseurope.17000.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Accepted: 09/05/2024] [Indexed: 09/18/2024]
Abstract
Background Surface topography has been shown to influence cell behavior and direct stromal cell differentiation into distinct lineages. Whereas this phenomenon has been verified in two-dimensional cultures, there is an urgent need for a thorough investigation of topography's role within a three-dimensional (3D) environment, as it better replicates the natural cellular environment. Methods A co-culture of Wharton's jelly-derived mesenchymal stem/stromal cells (WJ-MSCs) and human umbilical vein endothelial cells (HUVECs) was encapsulated in a 3D system consisting of a permselective liquefied environment containing freely dispersed spherical microparticles (spheres) or nanogrooved microdiscs (microdiscs). Microdiscs presenting 358 ± 23 nm grooves and 944 ± 49 nm ridges were produced via nanoimprinting of spherical polycaprolactone microparticles between water-soluble polyvinyl alcohol counter molds of nanogrooved templates. Spheres and microdiscs were cultured in vitro with umbilical cord-derived cells in a basal or osteogenic medium within liquefied capsules for 21 days. Results WJ-MSCs and HUVECs were successfully encapsulated within liquefied capsules containing spheres and microdiscs, ensuring high cellular viability. Results show an enhanced osteogenic differentiation in microdiscs compared to spheres, even in basal medium, evidenced by alkaline phosphatase activity and osteopontin expression. Conclusions This work suggests that the topographical features present in microdiscs induce the osteogenic differentiation of adhered WJ-MSCs along the contact guidance, without additional differentiation factors. The developed 3D bioencapsulation system comprising topographical features might be suitable for bone tissue engineering approaches with minimum in vitro manipulation.
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Affiliation(s)
- Mariana Carreira
- CICECO – Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Aveiro, Aveiro District, 3810-193, Portugal
| | - Manuel Pires-Santos
- CICECO – Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Aveiro, Aveiro District, 3810-193, Portugal
| | - Clara R Correia
- CICECO – Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Aveiro, Aveiro District, 3810-193, Portugal
| | - Sara Nadine
- CICECO – Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Aveiro, Aveiro District, 3810-193, Portugal
| | - João F Mano
- CICECO – Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Aveiro, Aveiro District, 3810-193, Portugal
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Zhang B, Hu Y, Du H, Han S, Ren L, Cheng H, Wang Y, Gao X, Zheng S, Cui Q, Tian L, Liu T, Sun J, Chai R. Tissue engineering strategies for spiral ganglion neuron protection and regeneration. J Nanobiotechnology 2024; 22:458. [PMID: 39085923 PMCID: PMC11293049 DOI: 10.1186/s12951-024-02742-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 07/25/2024] [Indexed: 08/02/2024] Open
Abstract
Cochlear implants can directly activate the auditory system's primary sensory neurons, the spiral ganglion neurons (SGNs), via circumvention of defective cochlear hair cells. This bypass restores auditory input to the brainstem. SGN loss etiologies are complex, with limited mammalian regeneration. Protecting and revitalizing SGN is critical. Tissue engineering offers a novel therapeutic strategy, utilizing seed cells, biomolecules, and scaffold materials to create a cellular environment and regulate molecular cues. This review encapsulates the spectrum of both human and animal research, collating the factors contributing to SGN loss, the latest advancements in the utilization of exogenous stem cells for auditory nerve repair and preservation, the taxonomy and mechanism of action of standard biomolecules, and the architectural components of scaffold materials tailored for the inner ear. Furthermore, we delineate the potential and benefits of the biohybrid neural interface, an incipient technology in the realm of implantable devices. Nonetheless, tissue engineering requires refined cell selection and differentiation protocols for consistent SGN quality. In addition, strategies to improve stem cell survival, scaffold biocompatibility, and molecular cue timing are essential for biohybrid neural interface integration.
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Affiliation(s)
- Bin Zhang
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Public Health, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, China
- Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China
| | - Yangnan Hu
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Public Health, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, China.
- Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China.
| | - Haoliang Du
- Department of Otolaryngology Head and Neck Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing University, Nanjing, 210008, China
| | - Shanying Han
- Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Lei Ren
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Public Health, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, China
| | - Hong Cheng
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Public Health, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, China
| | - Yusong Wang
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Public Health, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, China
| | - Xin Gao
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Public Health, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, China
| | - Shasha Zheng
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Public Health, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, China
| | - Qingyue Cui
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Public Health, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, China
| | - Lei Tian
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Public Health, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, China.
| | - Tingting Liu
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Public Health, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, China.
| | - Jiaqiang Sun
- Department of Otolaryngology-Head and Neck Surgery, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 230001, China.
| | - Renjie Chai
- State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Public Health, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, China.
- Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China.
- Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China.
- Department of Neurology, Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing, 100081, China.
- Institute for Stem Cell and Regeneration, Chinese Academy of Science, Beijing, China.
- Southeast University Shenzhen Research Institute, Shenzhen, 518063, China.
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10
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Wang X, Wang Y, Lu W, Qu J, Zhang Y, Ye J. Effectiveness and mechanisms of mesenchymal stem cell therapy in preclinical animal models of hepatic fibrosis: a systematic review and meta-analysis. Front Bioeng Biotechnol 2024; 12:1424253. [PMID: 39104627 PMCID: PMC11299041 DOI: 10.3389/fbioe.2024.1424253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Accepted: 06/26/2024] [Indexed: 08/07/2024] Open
Abstract
Background Liver damage due to long-term viral infection, alcohol consumption, autoimmune decline, and other factors could lead to the gradual development of liver fibrosis. Unfortunately, until now, there has been no effective treatment for liver fibrosis. Mesenchymal stem cells, as a promising new therapy for liver fibrosis, can slow the progression of fibrosis by migrating to the site of liver injury and by altering the microenvironment of the fibrotic area. Aim By including all relevant studies to date to comprehensively assess the efficacy of mesenchymal stem cells for the treatment of hepatic fibrosis and to explore considerations for clinical translation and therapeutic mechanisms. Methods Data sources included PubMed, Web of Science, Embase, and Cochrane Library, and were constructed until October 2023. Data for each study outcome indicator were extracted for comprehensive analysis. Results The overall meta-analysis showed that mesenchymal stem cells significantly improved liver function. Moreover, it inhibited the expression level of transforming growth factor-β [SMD = 4.21, 95% CI (3.02,5.40)], which in turn silenced hepatic stellate cells and significantly reduced the area of liver fibrosis [SMD = 3.61, 95% CI (1.41,5.81)]. Conclusion Several outcome indicators suggest that mesenchymal stem cells therapy is relatively reliable in the treatment of liver fibrosis. The therapeutic effect is cell dose-dependent over a range of doses, but not more effective at higher doses. Bone-marrow derived mesenchymal stem cells were more effective in treating liver fibrosis than mesenchymal stem cells from other sources. Systematic Review Registration Identifier CRD42022354768.
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Affiliation(s)
- Xuesong Wang
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
- School of Rehabilitation Medicine Gannan Medical University, Ganzhou, Jiangxi, China
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Ganzhou, Jiangxi, China
| | - Yue Wang
- College of Nursing, Gannan Medical University, Ganzhou, Jiangxi, China
| | - Wenming Lu
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
- School of Rehabilitation Medicine Gannan Medical University, Ganzhou, Jiangxi, China
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Ganzhou, Jiangxi, China
| | - Jiayang Qu
- Rehabilitation Assessment and Treatment Center, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Yang Zhang
- School of Rehabilitation Medicine Gannan Medical University, Ganzhou, Jiangxi, China
| | - Junsong Ye
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Ganzhou, Jiangxi, China
- Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, Jiangxi, China
- Jiangxi Provincal Key Laboratory of Tissue Engineering, Gannan Medical University, Ganzhou, Jiangxi, China
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11
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Subramanian A, Ip CHL, Qin W, Liu X, W D Carter S, Oguz G, Ramasamy A, E Illanes S, Biswas A, G Perron G, L Fee E, W L Li S, K Y Seah M, A Choolani M, W Kemp M. Simulated lunar microgravity transiently arrests growth and induces osteocyte-chondrocyte lineage differentiation in human Wharton's jelly stem cells. NPJ Microgravity 2024; 10:51. [PMID: 38704360 PMCID: PMC11069510 DOI: 10.1038/s41526-024-00397-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 04/08/2024] [Indexed: 05/06/2024] Open
Abstract
Human Wharton's jelly stem cells (hWJSCs) are multipotent stem cells that are extensively employed in biotechnology applications. However, the impact of simulated lunar microgravity (sμG) on the growth, differentiation, and viability of this cell population is incompletely characterized. We aimed to determine whether acute (72 h) exposure to sμG elicited changes in growth and lineage differentiation in hWJSCs and if putative changes were maintained once exposure to terrestrial gravity (1.0 G) was restored. hWJSCs were cultured under standard 1.0 G conditions prior to being passaged and cultured under sμG (0.16 G) using a random positioning machine. Relative to control, hWJSCs cultured under sμG exhibited marked reductions in growth but not viability. Cell population expression of characteristic stemness markers (CD 73, 90, 105) was significantly reduced under sμG conditions. hWJSCs had 308 significantly upregulated and 328 significantly downregulated genes when compared to 1.0 G culture conditions. Key markers of cell replication, including MKI67, were inhibited. Significant upregulation of osteocyte-chondrocyte lineage markers, including SERPINI1, MSX2, TFPI2, BMP6, COMP, TMEM119, LUM, HGF, CHI3L1 and SPP1, and downregulation of cell fate regulators, including DNMT1 and EZH2, were detected in sμG-exposed hWJSCs. When returned to 1.0 G for 3 days, sμG-exposed hWJSCs had accelerated growth, and expression of stemness markers increased, approaching normal (i.e. 95%) levels. Our data support earlier findings that acute sμG significantly reduces the cell division potential of hWJSCs and suggest that acute sμG-exposure induces reversible changes in cell growth accompanied by osteocyte-chondrocyte changes in lineage differentiation.
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Affiliation(s)
- Arjunan Subramanian
- Department of Obstetrics and Gynaecology, NUS Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore
| | - Chelsea Han Lin Ip
- Department of Obstetrics and Gynaecology, NUS Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore
| | - Wei Qin
- Department of Obstetrics and Gynecology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, No. 46 Chongxin Road, 541002, Guilin City, Guangxi Zhuang Autonomous Region, P. R. China
| | - Xiawen Liu
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital Guangzhou Medical University, 511436, Guangzhou, P.R. China
| | - Sean W D Carter
- Department of Obstetrics and Gynaecology, NUS Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore
| | - Gokce Oguz
- Genome Institute of Singapore (GIS). Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome #02-01, Singapore, 138632, Republic of Singapore
| | - Adaikalavan Ramasamy
- Genome Institute of Singapore (GIS). Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome #02-01, Singapore, 138632, Republic of Singapore
| | - Sebastian E Illanes
- Department of Obstetrics and Gynaecology, NUS Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore
- Department of Obstetrics and Gynecology, Faculty of Medicine, Universidad de los Andes, Santiago, 7620001, Chile
- IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile
| | - Arijit Biswas
- Department of Obstetrics and Gynaecology, NUS Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore
- Department of Obstetrics and Gynaecology, National University Hospital, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore
| | - Gabriel G Perron
- Center for Genomics and Systems Biology, New York University, New York, NY, 10003, USA
| | - Erin L Fee
- Division of Obstetrics and Gynaecology, University of Western Australia, Perth, WA, Australia
- Women and Infants Research Foundation, King Edward Memorial Hospital, Subiaco, WA, Australia
| | - Sarah W L Li
- Department of Obstetrics and Gynaecology, NUS Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore
- Department of Obstetrics and Gynaecology, National University Hospital, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore
| | - Michelle K Y Seah
- Department of Obstetrics and Gynaecology, NUS Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore
| | - Mahesh A Choolani
- Department of Obstetrics and Gynaecology, NUS Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore.
- Department of Obstetrics and Gynaecology, National University Hospital, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore.
| | - Matthew W Kemp
- Department of Obstetrics and Gynaecology, NUS Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore.
- Department of Obstetrics and Gynaecology, National University Hospital, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore.
- Division of Obstetrics and Gynaecology, University of Western Australia, Perth, WA, Australia.
- Women and Infants Research Foundation, King Edward Memorial Hospital, Subiaco, WA, Australia.
- Centre for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, 980-8574, Japan.
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Sarma S, Deka DJ, Rajak P, Laloo D, Das T, Chetia P, Saha D, Bharali A, Deka B. Potential injectable hydrogels as biomaterials for central nervous system injury: A narrative review. IBRAIN 2023; 9:402-420. [PMID: 38680508 PMCID: PMC11045191 DOI: 10.1002/ibra.12137] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 10/20/2023] [Accepted: 10/27/2023] [Indexed: 05/01/2024]
Abstract
Numerous modalities exist through which the central nervous system (CNS) may sustain injury or impairment, encompassing traumatic incidents, stroke occurrences, and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Presently available pharmacological and therapeutic interventions are incapable of restoring or regenerating damaged CNS tissue, leading to substantial unmet clinical needs among patients with CNS ailments or injuries. To address and facilitate the recovery of the impaired CNS, cell-based repair strategies encompass multiple mechanisms, such as neuronal replacement, therapeutic factor secretion, and the promotion of host brain plasticity. Despite the progression of cell-based CNS reparation as a therapeutic strategy throughout the years, substantial barriers have impeded its widespread implementation in clinical settings. The integration of cell technologies with advancements in regenerative medicine utilizing biomaterials and tissue engineering has recently facilitated the surmounting of several of these impediments. This comprehensive review presents an overview of distinct CNS conditions necessitating cell reparation, in addition to exploring potential biomaterial methodologies that enhance the efficacy of treating brain injuries.
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Affiliation(s)
- Santa Sarma
- Girijananda Chowdhury Institute of Pharmaceutical ScienceAssam Science and Technology UniversityGuwahatiAssamIndia
| | - Dhruva J. Deka
- Girijananda Chowdhury Institute of Pharmaceutical ScienceAssam Science and Technology UniversityGuwahatiAssamIndia
| | - Prakash Rajak
- Department of Pharmaceutical SciencesDibrugarh UniversityDibrugarhAssamIndia
| | - Damiki Laloo
- School of Pharmaceutical SciencesGirijananda Chowdhury UniversityGuwahatiAssamIndia
| | - Trishna Das
- School of Pharmaceutical SciencesGirijananda Chowdhury UniversityGuwahatiAssamIndia
| | - Purbajit Chetia
- Department of PharmacologyNETES Institute of Pharmaceutical Science, Nemcare Group of Institutes, MirzaGuwahatiAssamIndia
| | - Dipankar Saha
- School of Pharmaceutical SciencesGirijananda Chowdhury UniversityGuwahatiAssamIndia
| | - Alakesh Bharali
- Department of Pharmaceutical SciencesDibrugarh UniversityDibrugarhAssamIndia
- School of Pharmaceutical SciencesGirijananda Chowdhury UniversityGuwahatiAssamIndia
| | - Bhargab Deka
- School of Pharmaceutical SciencesGirijananda Chowdhury UniversityGuwahatiAssamIndia
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Bruschettini M, Badura A, Romantsik O. Stem cell-based interventions for the treatment of stroke in newborn infants. Cochrane Database Syst Rev 2023; 11:CD015582. [PMID: 37994736 PMCID: PMC10666199 DOI: 10.1002/14651858.cd015582.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2023]
Abstract
BACKGROUND Perinatal stroke refers to a diverse but specific group of cerebrovascular diseases that occur between 20 weeks of fetal life and 28 days of postnatal life. Acute treatment options for perinatal stroke are limited supportive care, such as controlling hypoglycemia and seizures. Stem cell-based therapies offer a potential therapeutic approach to repair, restore, or regenerate injured brain tissue. Preclinical findings have culminated in ongoing human neonatal studies. OBJECTIVES To evaluate the benefits and harms of stem cell-based interventions for the treatment of stroke in newborn infants compared to control (placebo or no treatment) or stem-cell based interventions of a different type or source. SEARCH METHODS We searched CENTRAL, PubMed, Embase, and three trials registries in February 2023. We planned to search the reference lists of included studies and relevant systematic reviews for studies not identified by the database searches. SELECTION CRITERIA We attempted to include randomized controlled trials, quasi-randomized controlled trials, and cluster trials that evaluated any of the following comparisons. • Stem cell-based interventions (any type) versus control (placebo or no treatment) • Mesenchymal stem/stromal cells (MSCs) of a specifictype (e.g. number of doses or passages) or source (e.g. autologous/allogeneic or bone marrow/cord) versus MSCs of another type or source • Stem cell-based interventions (other than MSCs) of a specific type (e.g. mononuclear cells, oligodendrocyte progenitor cells, neural stem cells, hematopoietic stem cells, or induced pluripotent stem cell-derived cells) or source (e.g. autologous/allogeneic or bone marrow/cord) versus stem cell-based interventions (other than MSCs) of another type or source • MSCs versus stem cell-based interventions other than MSCs We planned to include all types of transplantation regardless of cell source (bone marrow, cord blood, Wharton's jelly, placenta, adipose tissue, peripheral blood), type of graft (autologous or allogeneic), and dose. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were all-cause neonatal mortality, major neurodevelopmental disability, and immune rejection or any serious adverse event. Our secondary outcomes included all-cause mortality prior to first hospital discharge, seizures, adverse effects, and death or major neurodevelopmental disability at 18 to 24 months of age. We planned to use GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS We identified no completed or ongoing randomized trials that met our inclusion criteria. We excluded three studies: two were phase 1 trials, and one included newborn infants with conditions other than stroke (i.e. cerebral ischemia and anemia). Among the three excluded studies, we identified the first phase 1 trial on the use of stem cells for neonatal stroke. It reported that a single intranasal application of bone marrow-derived MSCs in term neonates with a diagnosis of perinatal arterial ischemic stroke (PAIS) was feasible and apparently not associated with severe adverse events. However, the trial included only 10 infants, and follow-up was limited to three months. AUTHORS' CONCLUSIONS No evidence is currently available to evaluate the benefits and harms of stem cell-based interventions for treatment of stroke in newborn infants. We identified no ongoing studies. Future clinical trials should focus on standardizing the timing and method of cell delivery and cell processing to optimize the therapeutic potential of stem cell-based interventions and safety profiles. Phase 1 and large animal studies might provide the groundwork for future randomized trials. Outcome measures should include all-cause mortality, major neurodevelopmental disability and immune rejection, and any other serious adverse events.
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Affiliation(s)
- Matteo Bruschettini
- Paediatrics, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden
- Cochrane Sweden, Department of Research and Education, Lund University, Skåne University Hospital, Lund, Sweden
| | - Anna Badura
- Department of Neonatology, University Children's Hospital Regensburg, Hospital St Hedwig of the Order of St John, University of Regensburg, Regensburg, Germany
| | - Olga Romantsik
- Paediatrics, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden
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14
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Tang XL, Nasr M, Zheng S, Zoubul T, Stephan JK, Uchida S, Singhal R, Khan A, Gumpert A, Bolli R, Wysoczynski M. Bone Marrow and Wharton's Jelly Mesenchymal Stromal Cells are Ineffective for Myocardial Repair in an Immunodeficient Rat Model of Chronic Ischemic Cardiomyopathy. Stem Cell Rev Rep 2023; 19:2429-2446. [PMID: 37500831 PMCID: PMC10579184 DOI: 10.1007/s12015-023-10590-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/09/2023] [Indexed: 07/29/2023]
Abstract
BACKGROUND Although cell therapy provides benefits for outcomes of heart failure, the most optimal cell type to be used clinically remains unknown. Most of the cell products used for therapy in humans require in vitro expansion to obtain a suitable number of cells for treatment; however, the clinical background of the donor and limited starting material may result in the impaired proliferative and reparative capacity of the cells expanded in vitro. Wharton's jelly mesenchymal cells (WJ MSCs) provide a multitude of advantages over adult tissue-derived cell products for therapy. These include large starting tissue material, superior proliferative capacity, and disease-free donors. Thus, WJ MSC if effective would be the most optimal cell source for clinical use. OBJECTIVES This study evaluated the therapeutic efficacy of Wharton's jelly (WJ) and bone marrow (BM) mesenchymal stromal cells (MSCs) in chronic ischemic cardiomyopathy in rats. METHODS Human WJ MSCs and BM MSCs were expanded in vitro, characterized, and evaluated for therapeutic efficacy in a immunodeficient rat model of ischemic cardiomyopathy. Cardiac function was evaluated with hemodynamics and echocardiography. The extent of cardiac fibrosis, hypertrophy, and inflammation was assessed with histological analysis. RESULTS In vitro analysis revealed that WJ MSCs and BM MSCs are morphologically and immunophenotypically indistinguishable. Nevertheless, the functional analysis showed that WJ MSCs have a superior proliferative capacity, less senescent phenotype, and distinct transcriptomic profile compared to BM MSC. WJ MSCs and BM MSC injected in rat hearts chronically after MI produced a small, but not significant improvement in heart structure and function. Histological analysis showed no difference in the scar size, collagen content, cardiomyocyte cross-sectional area, and immune cell count. CONCLUSIONS Human WJ and BM MSC have a small but not significant effect on cardiac structure and function when injected intramyocardially in immunodeficient rats chronically after MI.
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Affiliation(s)
- Xian-Liang Tang
- Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, KY, USA
| | - Marjan Nasr
- Center for Cardiometabolic Science, University of Louisville School of Medicine, 580 South Preston St. - Rm 204B, Louisville, KY, 40202, USA
| | - Shirong Zheng
- Center for Cardiometabolic Science, University of Louisville School of Medicine, 580 South Preston St. - Rm 204B, Louisville, KY, 40202, USA
| | - Taylor Zoubul
- Center for Cardiometabolic Science, University of Louisville School of Medicine, 580 South Preston St. - Rm 204B, Louisville, KY, 40202, USA
| | - Jonah K Stephan
- Center for Cardiometabolic Science, University of Louisville School of Medicine, 580 South Preston St. - Rm 204B, Louisville, KY, 40202, USA
| | - Shizuka Uchida
- Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Richa Singhal
- Center for Cardiometabolic Science, University of Louisville School of Medicine, 580 South Preston St. - Rm 204B, Louisville, KY, 40202, USA
| | - Aisha Khan
- Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Anna Gumpert
- Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, KY, USA
| | - Roberto Bolli
- Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, KY, USA
| | - Marcin Wysoczynski
- Center for Cardiometabolic Science, University of Louisville School of Medicine, 580 South Preston St. - Rm 204B, Louisville, KY, 40202, USA.
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15
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Russo E, Alberti G, Corrao S, Borlongan CV, Miceli V, Conaldi PG, Di Gaudio F, La Rocca G. The Truth Is Out There: Biological Features and Clinical Indications of Extracellular Vesicles from Human Perinatal Stem Cells. Cells 2023; 12:2347. [PMID: 37830562 PMCID: PMC10571796 DOI: 10.3390/cells12192347] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 09/14/2023] [Accepted: 09/19/2023] [Indexed: 10/14/2023] Open
Abstract
The potential of perinatal tissues to provide cellular populations to be used in different applications of regenerative medicine is well established. Recently, the efforts of researchers are being addressed regarding the evaluation of cell products (secreted molecules or extracellular vesicles, EVs) to be used as an alternative to cellular infusion. The data regarding the effective recapitulation of most perinatal cells' properties by their secreted complement point in this direction. EVs secreted from perinatal cells exhibit key therapeutic effects such as tissue repair and regeneration, the suppression of inflammatory responses, immune system modulation, and a variety of other functions. Although the properties of EVs from perinatal derivatives and their significant potential for therapeutic success are amply recognized, several challenges still remain that need to be addressed. In the present review, we provide an up-to-date analysis of the most recent results in the field, which can be addressed in future research in order to overcome the challenges that are still present in the characterization and utilization of the secreted complement of perinatal cells and, in particular, mesenchymal stromal cells.
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Affiliation(s)
- Eleonora Russo
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy; (E.R.); (G.A.)
| | - Giusi Alberti
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy; (E.R.); (G.A.)
| | - Simona Corrao
- Research Department, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy; (S.C.); (V.M.); (P.G.C.)
| | - Cesar V. Borlongan
- Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USA;
| | - Vitale Miceli
- Research Department, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy; (S.C.); (V.M.); (P.G.C.)
| | - Pier Giulio Conaldi
- Research Department, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy; (S.C.); (V.M.); (P.G.C.)
| | - Francesca Di Gaudio
- Department of Health Promotion, Maternal-Infantile Care, Excellence Internal and Specialist Medicine “G. D’Alessandro” (PROMISE), University of Palermo, 90127 Palermo, Italy;
| | - Giampiero La Rocca
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy; (E.R.); (G.A.)
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16
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Drobiova H, Sindhu S, Ahmad R, Haddad D, Al-Mulla F, Al Madhoun A. Wharton's jelly mesenchymal stem cells: a concise review of their secretome and prospective clinical applications. Front Cell Dev Biol 2023; 11:1211217. [PMID: 37440921 PMCID: PMC10333601 DOI: 10.3389/fcell.2023.1211217] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 06/13/2023] [Indexed: 07/15/2023] Open
Abstract
Accumulating evidence indicates that most primary Wharton's jelly mesenchymal stem cells (WJ-MSCs) therapeutic potential is due to their paracrine activity, i.e., their ability to modulate their microenvironment by releasing bioactive molecules and factors collectively known as secretome. These bioactive molecules and factors can either be released directly into the surrounding microenvironment or can be embedded within the membrane-bound extracellular bioactive nano-sized (usually 30-150 nm) messenger particles or vesicles of endosomal origin with specific route of biogenesis, known as exosomes or carried by relatively larger particles (100 nm-1 μm) formed by outward blebbing of plasma membrane called microvesicles (MVs); exosomes and MVs are collectively known as extracellular vesicles (EVs). The bioactive molecules and factors found in secretome are of various types, including cytokines, chemokines, cytoskeletal proteins, integrins, growth factors, angiogenic mediators, hormones, metabolites, and regulatory nucleic acid molecules. As expected, the secretome performs different biological functions, such as immunomodulation, tissue replenishment, cellular homeostasis, besides possessing anti-inflammatory and anti-fibrotic effects. This review highlights the current advances in research on the WJ-MSCs' secretome and its prospective clinical applications.
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Affiliation(s)
- Hana Drobiova
- Human Genetics Unit, Department of Pathology, College of Medicine, Kuwait University, Jabriya, Kuwait
| | - Sardar Sindhu
- Animal and Imaging Core Facilities, Dasman Diabetes Institute, Dasman, Kuwait
- Department of Immunology and Microbiology, Dasman Diabetes Institute, Dasman, Kuwait
| | - Rasheed Ahmad
- Department of Immunology and Microbiology, Dasman Diabetes Institute, Dasman, Kuwait
| | - Dania Haddad
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait
| | - Fahd Al-Mulla
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait
| | - Ashraf Al Madhoun
- Animal and Imaging Core Facilities, Dasman Diabetes Institute, Dasman, Kuwait
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait
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Rosner M, Horer S, Feichtinger M, Hengstschläger M. Multipotent fetal stem cells in reproductive biology research. Stem Cell Res Ther 2023; 14:157. [PMID: 37287077 DOI: 10.1186/s13287-023-03379-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 05/16/2023] [Indexed: 06/09/2023] Open
Abstract
Due to the limited accessibility of the in vivo situation, the scarcity of the human tissue, legal constraints, and ethical considerations, the underlying molecular mechanisms of disorders, such as preeclampsia, the pathological consequences of fetomaternal microchimerism, or infertility, are still not fully understood. And although substantial progress has already been made, the therapeutic strategies for reproductive system diseases are still facing limitations. In the recent years, it became more and more evident that stem cells are powerful tools for basic research in human reproduction and stem cell-based approaches moved into the center of endeavors to establish new clinical concepts. Multipotent fetal stem cells derived from the amniotic fluid, amniotic membrane, chorion leave, Wharton´s jelly, or placenta came to the fore because they are easy to acquire, are not associated with ethical concerns or covered by strict legal restrictions, and can be banked for autologous utilization later in life. Compared to adult stem cells, they exhibit a significantly higher differentiation potential and are much easier to propagate in vitro. Compared to pluripotent stem cells, they harbor less mutations, are not tumorigenic, and exhibit low immunogenicity. Studies on multipotent fetal stem cells can be invaluable to gain knowledge on the development of dysfunctional fetal cell types, to characterize the fetal stem cells migrating into the body of a pregnant woman in the context of fetomaternal microchimerism, and to obtain a more comprehensive picture of germ cell development in the course of in vitro differentiation experiments. The in vivo transplantation of fetal stem cells or their paracrine factors can mediate therapeutic effects in preeclampsia and can restore reproductive organ functions. Together with the use of fetal stem cell-derived gametes, such strategies could once help individuals, who do not develop functional gametes, to conceive genetically related children. Although there is still a long way to go, these developments regarding the usage of multipotent fetal stem cells in the clinic should continuously be accompanied by a wide and detailed ethical discussion.
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Affiliation(s)
- Margit Rosner
- Institute of Medical Genetics, Center for Pathobiochemistry and Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria
| | - Stefanie Horer
- Institute of Medical Genetics, Center for Pathobiochemistry and Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria
| | | | - Markus Hengstschläger
- Institute of Medical Genetics, Center for Pathobiochemistry and Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria.
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18
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Yang X, Li Q, Liu W, Zong C, Wei L, Shi Y, Han Z. Mesenchymal stromal cells in hepatic fibrosis/cirrhosis: from pathogenesis to treatment. Cell Mol Immunol 2023; 20:583-599. [PMID: 36823236 PMCID: PMC10229624 DOI: 10.1038/s41423-023-00983-5] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 01/29/2023] [Indexed: 02/25/2023] Open
Abstract
Hepatic fibrosis/cirrhosis is a significant health burden worldwide, resulting in liver failure or hepatocellular carcinoma (HCC) and accounting for many deaths each year. The pathogenesis of hepatic fibrosis/cirrhosis is very complex, which makes treatment challenging. Endogenous mesenchymal stromal cells (MSCs) have been shown to play pivotal roles in the pathogenesis of hepatic fibrosis. Paradoxically, exogenous MSCs have also been used in clinical trials for liver cirrhosis, and their effectiveness has been observed in most completed clinical trials. There are still many issues to be resolved to promote the use of MSCs in the clinic in the future. In this review, we will examine the controversial role of MSCs in the pathogenesis and treatment of hepatic fibrosis/cirrhosis. We also investigated the clinical trials involving MSCs in liver cirrhosis, summarized the parameters that need to be standardized, and discussed how to promote the use of MSCs from a clinical perspective.
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Affiliation(s)
- Xue Yang
- Department of Tumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Naval Medical University, Shanghai, 200438, China
- Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education, Eastern Hepatobiliary Surgery Hospital/National Center for Liver Cancer, Naval Medical University, Shanghai, 200438, China
- The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, State Key Laboratory of Radiation Medicine and Protection, Key Laboratory of Stem Cells and Medical Biomaterials of Jiangsu Province, Medical College of Soochow University, Soochow University, Suzhou, 215000, China
- Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy
| | - Qing Li
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
| | - Wenting Liu
- Department of Tumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Naval Medical University, Shanghai, 200438, China
- Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education, Eastern Hepatobiliary Surgery Hospital/National Center for Liver Cancer, Naval Medical University, Shanghai, 200438, China
| | - Chen Zong
- Department of Tumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Naval Medical University, Shanghai, 200438, China
- Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education, Eastern Hepatobiliary Surgery Hospital/National Center for Liver Cancer, Naval Medical University, Shanghai, 200438, China
| | - Lixin Wei
- Department of Tumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Naval Medical University, Shanghai, 200438, China
- Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education, Eastern Hepatobiliary Surgery Hospital/National Center for Liver Cancer, Naval Medical University, Shanghai, 200438, China
| | - Yufang Shi
- The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, State Key Laboratory of Radiation Medicine and Protection, Key Laboratory of Stem Cells and Medical Biomaterials of Jiangsu Province, Medical College of Soochow University, Soochow University, Suzhou, 215000, China.
- Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy.
| | - Zhipeng Han
- Department of Tumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Naval Medical University, Shanghai, 200438, China.
- Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education, Eastern Hepatobiliary Surgery Hospital/National Center for Liver Cancer, Naval Medical University, Shanghai, 200438, China.
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Cochrane Neonatal Group, Bruschettini M, Badura A, Romantsik O. Stem cell‐based interventions for the treatment of stroke in newborn infants. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2023; 2023:CD015582. [PMCID: PMC9933426 DOI: 10.1002/14651858.cd015582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/18/2023]
Abstract
This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and harms of stem cell‐based interventions for the treatment of stroke in newborn infants compared to control (placebo or no treatment) or stem‐cell based interventions of a different type or source.
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Affiliation(s)
| | - Matteo Bruschettini
- Department of Clinical Sciences Lund, PaediatricsLund University, Skåne University HospitalLundSweden,Cochrane SwedenLund University, Skåne University HospitalLundSweden
| | | | - Olga Romantsik
- Department of Clinical Sciences Lund, PaediatricsLund University, Skåne University HospitalLundSweden
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20
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Romantsik O, Moreira A, Thébaud B, Ådén U, Ley D, Bruschettini M. Stem cell-based interventions for the prevention and treatment of intraventricular haemorrhage and encephalopathy of prematurity in preterm infants. Cochrane Database Syst Rev 2023; 2:CD013201. [PMID: 36790019 PMCID: PMC9932000 DOI: 10.1002/14651858.cd013201.pub3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/16/2023]
Abstract
BACKGROUND Germinal matrix-intraventricular haemorrhage (GMH-IVH) and encephalopathy of prematurity (EoP) remain substantial issues in neonatal intensive care units worldwide. Current therapies to prevent or treat these conditions are limited. Stem cell-based therapies offer a potential therapeutic approach to repair, restore, or regenerate injured brain tissue. These preclinical findings have now culminated in ongoing human neonatal studies. This is an update of the 2019 review, which did not include EoP. OBJECTIVES To evaluate the benefits and harms of stem cell-based interventions for prevention or treatment of GM-IVH and EoP in preterm infants. SEARCH METHODS We used standard, extensive Cochrane search methods. The latest search was April 2022. SELECTION CRITERIA We attempted to include randomised controlled trials, quasi-randomised controlled trials, and cluster trials comparing 1. stem cell-based interventions versus control; 2. mesenchymal stromal cells (MSCs) of type or source versus MSCs of other type or source; 3. stem cell-based interventions other than MSCs of type or source versus stem cell-based interventions other than MSCs of other type or source; or 4. MSCs versus stem cell-based interventions other than MSCs. For prevention studies, we included extremely preterm infants (less than 28 weeks' gestation), 24 hours of age or less, without ultrasound diagnosis of GM-IVH or EoP; for treatment studies, we included preterm infants (less than 37 weeks' gestation), of any postnatal age, with ultrasound diagnosis of GM-IVH or with EoP. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were 1. all-cause neonatal mortality, 2. major neurodevelopmental disability, 3. GM-IVH, 4. EoP, and 5. extension of pre-existing non-severe GM-IVH or EoP. We planned to use GRADE to assess certainty of evidence for each outcome. MAIN RESULTS We identified no studies that met our inclusion criteria. Three studies are currently registered and ongoing. Phase 1 trials are described in the 'Excluded studies' section. AUTHORS' CONCLUSIONS No evidence is currently available to evaluate the benefits and harms of stem cell-based interventions for treatment or prevention of GM-IVH or EoP in preterm infants. We identified three ongoing studies, with a sample size range from 20 to 200. In two studies, autologous cord blood mononuclear cells will be administered to extremely preterm infants via the intravenous route; in one, intracerebroventricular injection of MSCs will be administered to preterm infants up to 34 weeks' gestational age.
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Affiliation(s)
- Olga Romantsik
- Department of Clinical Sciences Lund, Paediatrics, Lund University, Skåne University Hospital, Lund, Sweden
| | - Alvaro Moreira
- Pediatrics, Division of Neonatology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
| | - Bernard Thébaud
- Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Canada
- Ottawa Hospital Research Institute, Sprott Centre for Stem Cell Research, Ottawa, Canada
- Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada
| | - Ulrika Ådén
- Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
| | - David Ley
- Department of Clinical Sciences Lund, Paediatrics, Lund University, Skåne University Hospital, Lund, Sweden
| | - Matteo Bruschettini
- Department of Clinical Sciences Lund, Paediatrics, Lund University, Skåne University Hospital, Lund, Sweden
- Cochrane Sweden, Lund University, Skåne University Hospital, Lund, Sweden
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21
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Liu YJ, Miao HB, Lin S, Chen Z. Current Progress in Treating Systemic Lupus Erythematosus Using Exosomes/MicroRNAs. Cell Transplant 2023; 32:9636897221148775. [PMID: 36661068 PMCID: PMC9903023 DOI: 10.1177/09636897221148775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease associated with impaired organ functions that can seriously affect the daily life of patients. Recent SLE therapies frequently elicit adverse reactions and side effects in patients, and clinical heterogeneity is considerable. Mesenchymal stromal cells (MSCs) have anti-inflammatory, tissue repair, and immunomodulatory properties. Their ability to treat autoimmune diseases largely depends on secreted extracellular vesicles, especially exosomes. The effects of exosomes and microRNAs (miRNAs) on SLE have recently attracted interest. This review summarizes the applications of MSCs derived from bone marrow, adipocyte tissue, umbilical cord, synovial membrane, and gingival tissue, as well as exosomes to treating SLE and the key roles of miRNAs. The efficacy of MSCs infusion in SLE patients with impaired autologous MSCs are reviewed, and the potential of exosomes and their contents as drug delivery vectors for treating SLE and other autoimmune diseases in the future are briefly described.
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Affiliation(s)
- Yi-jing Liu
- Department of Rheumatology and Immunology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Hai-bing Miao
- Department of Rheumatology and Immunology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Shu Lin
- Centre of Neurological and Metabolic Research, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China,Group of Neuroendocrinology, Garvan Institute of Medical Research, Sydney, NSW, Australia
| | - Zhen Chen
- Department of Rheumatology and Immunology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China,Zhen Chen, Department of Rheumatology and Immunology, The Second Affiliated Hospital of Fujian Medical University, 34 Zhongshan Road, Quanzhou 362000, Fujian, P.R. China.
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22
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Dama G, Du J, Zhu X, Liu Y, Lin J. Bone marrow-derived mesenchymal stem cells: A promising therapeutic option for the treatment of diabetic foot ulcers. Diabetes Res Clin Pract 2023; 195:110201. [PMID: 36493913 DOI: 10.1016/j.diabres.2022.110201] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 08/31/2022] [Accepted: 12/01/2022] [Indexed: 12/12/2022]
Abstract
Chronic wounds fail to heal through the three normal stages of healing (inflammatory, proliferative, and remodelling), resulting in a chronic tissue injury that is not repaired within the average time limit. Patients suffering from type 1 and type 2 diabetes are prone to develop diabetic foot ulcers (DFUs), which commonly develop into chronic wounds that are non treatable with conventional therapies. DFU develops due to various risk factors, such as peripheral neuropathy, peripheral vascular disease, arterial insufficiency, foot deformities, trauma and impaired resistance to infection. DFUs have gradually become a major problem in the health care system worldwide. In this review, we not only focus on the pathogenesis of DFU but also comprehensively summarize the outcomes of preclinical and clinical studies thus far and the potential therapeutic mechanism of bone marrow-derived mesenchymal stem cells (BMSCs) for the treatment of DFU. Based on the published results, BMSC transplantation can contribute to wound healing through growth factor secretion, anti-inflammation, differentiation into tissue-specific cells, neovascularization, re-epithelialization and angiogenesis in DFUs. Moreover, clinical trials showed that BMSC treatment in patients with diabetic ulcers improved ulcer healing and the ankle-brachial index, ameliorated pain scores, and enhanced claudication walking distances with no reported complications. In conclusion, although BMSC transplantation exhibits promising therapeutic potential in DFU treatment, additional studies should be performed to confirm their efficacy and long-term safety in DFU patients.
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Affiliation(s)
- Ganesh Dama
- Stem Cell and Biotherapy Engineering Research Center of Henan, Henan Joint International Research Laboratory of Stem Cell Medicine, Xinxiang Medical University, East of JinSui Road #601, 453003 Xinxiang, China; Department of Community Health, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Malaysia
| | - Jiang Du
- Stem Cell and Biotherapy Engineering Research Center of Henan, Henan Joint International Research Laboratory of Stem Cell Medicine, Xinxiang Medical University, East of JinSui Road #601, 453003 Xinxiang, China; College of Medical Engineering, Xinxiang Medical University, East of JinSui Road #601, 453003 Xinxiang, China
| | - Xinxing Zhu
- Stem Cell and Biotherapy Engineering Research Center of Henan, Henan Joint International Research Laboratory of Stem Cell Medicine, Xinxiang Medical University, East of JinSui Road #601, 453003 Xinxiang, China; College of Medical Engineering, Xinxiang Medical University, East of JinSui Road #601, 453003 Xinxiang, China
| | - Yanli Liu
- Stem Cell and Biotherapy Engineering Research Center of Henan, Henan Joint International Research Laboratory of Stem Cell Medicine, Xinxiang Medical University, East of JinSui Road #601, 453003 Xinxiang, China; College of Life Sciences and Technology, Xinxiang Medical University, East of JinSui Road #601, 453003 Xinxiang, China.
| | - Juntang Lin
- Stem Cell and Biotherapy Engineering Research Center of Henan, Henan Joint International Research Laboratory of Stem Cell Medicine, Xinxiang Medical University, East of JinSui Road #601, 453003 Xinxiang, China; College of Medical Engineering, Xinxiang Medical University, East of JinSui Road #601, 453003 Xinxiang, China; College of Life Sciences and Technology, Xinxiang Medical University, East of JinSui Road #601, 453003 Xinxiang, China.
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23
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Chua AWC, Guo D, Tan JC, Lim FTW, Ong CT, Masilamani J, Lim TKH, Hwang WYK, Lim IJ, Chen J, Phan TT, Fan X. Intraperitoneally Delivered Umbilical Cord Lining Mesenchymal Stromal Cells Improve Survival and Kidney Function in Murine Lupus via Myeloid Pathway Targeting. Int J Mol Sci 2022; 24:365. [PMID: 36613807 PMCID: PMC9820333 DOI: 10.3390/ijms24010365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 12/16/2022] [Accepted: 12/16/2022] [Indexed: 12/28/2022] Open
Abstract
To determine the therapeutic efficacy of human umbilical cord lining mesenchymal stromal cells (CL-MSCs) (US Patent number 9,737,568) in lupus-prone MRL/lpr (Faslpr) mice and elucidate its working mechanisms. A total of 4 doses of (20-25) × 106 cells/kg of CL-MSCs was given to 16-week-old female Faslpr mice by intraperitoneal injection. Three subsequent doses were given on 17 weeks, 18 weeks, and 22 weeks, respectively. Six-week-old Faslpr mice were used as disease pre-onset controls. Mice were monitored for 10 weeks. Mouse kidney function was evaluated by examining complement component 3 (C3) deposition, urinary albumin-to-creatinine ratio (ACR), and lupus nephritis (LN) activity and chronicity. Working mechanisms were elucidated by flow cytometry, Luminex/ELISA (detection of anti-dsDNA and isotype antibodies), and RNA sequencing. CL-MSCs improved mice survival and kidney function by reducing LN activity and chronicity and lymphocyte infiltration over 10 weeks. CL-MSCs also reduced urinary ACR, renal complement C3 deposition, anti-dsDNA, and isotype antibodies that include IgA, IgG1, IgG2a, IgG2b, and IgM. Immune and cytokine profiling demonstrated that CL-MSCs dampened inflammation by suppressing splenic neutrophils and monocytes/macrophages, reducing plasma IL-6, IL-12, and CXCL1 and stabilizing plasma interferon-γ and TNF-α. RNA sequencing further showed that CL-MSCs mediated immunomodulation via concerted action of pro-proinflammatory cytokine-induced chemokines and production of nitric oxide in macrophages. CL-MSCs may provide a novel myeloid (neutrophils and monocytes/macrophages)-targeting therapy for SLE.
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Affiliation(s)
- Alvin Wen Choong Chua
- Department of Plastic, Reconstructive and Aesthetic Surgery, Singapore General Hospital, Singapore 169856, Singapore
| | - Dianyang Guo
- Department of Clinical Translational Research, Singapore General Hospital, Singapore 169608, Singapore
| | - Jia Chi Tan
- Single-Cell Computational Immunology, Singapore Immunology Network, Singapore 138668, Singapore
| | - Frances Ting Wei Lim
- Department of Clinical Translational Research, Singapore General Hospital, Singapore 169608, Singapore
| | - Chee Tian Ong
- CellResearch Corporation Pte Ltd., Singapore 048943, Singapore
| | | | - Tony Kiat Hon Lim
- Department of Anatomical Pathology, Singapore General Hospital, Singapore 169856, Singapore
| | - William Ying Khee Hwang
- Department of Hematology, Singapore General Hospital, Singapore 169856, Singapore
- National Cancer Centre Singapore, Singapore 169610, Singapore
| | - Ivor Jiun Lim
- CellResearch Corporation Pte Ltd., Singapore 048943, Singapore
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | - Jinmiao Chen
- Single-Cell Computational Immunology, Singapore Immunology Network, Singapore 138668, Singapore
| | - Toan Thang Phan
- CellResearch Corporation Pte Ltd., Singapore 048943, Singapore
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | - Xiubo Fan
- Department of Clinical Translational Research, Singapore General Hospital, Singapore 169608, Singapore
- SingHealth Duke-NUS Medicine Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore
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24
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Effects of green light-emitting diode irradiation on neural differentiation of human umbilical cord matrix-derived mesenchymal cells; Involvement of MAPK pathway. Biochem Biophys Res Commun 2022; 637:259-266. [DOI: 10.1016/j.bbrc.2022.11.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 11/06/2022] [Accepted: 11/10/2022] [Indexed: 11/17/2022]
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25
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Xia P, Shi Y, Wang X, Li X. Advances in the application of low-intensity pulsed ultrasound to mesenchymal stem cells. Stem Cell Res Ther 2022; 13:214. [PMID: 35619156 PMCID: PMC9137131 DOI: 10.1186/s13287-022-02887-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Accepted: 05/03/2022] [Indexed: 11/10/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are stem cells that exhibit self-renewal capacity and multi-directional differentiation potential. They can be extracted from the bone marrow and umbilical cord, as well as adipose, amnion, and other tissues. They are widely used in tissue engineering and are currently considered an important source of cells in the field of regenerative medicine. Since certain limitations, such as an insufficient cell source, mature differentiation, and low transplantation efficiency, are still associated with MSCs, researchers have currently focused on improving the efficacy of MSCs. Low-intensity pulsed ultrasound (LIPUS) has mechanical, cavitation, and thermal effects that can produce different biological effects on organs, tissues, and cells. It can be used for fracture treatment, cartilage repair, and stem cell applications. An in-depth study of the role and mechanism of action of LIPUS in MSC treatment would promote our understanding of LIPUS and promote research in this field. In this article, we have reviewed the progress in research on the use of LIPUS with various MSCs and comprehensively discussed the progress in the use of LIPUS for promoting the proliferation, differentiation, and migration of MSCs, as well as its future prospects.
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Affiliation(s)
- Peng Xia
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
| | - Yi Shi
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
| | - Xiaoju Wang
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
| | - Xueping Li
- Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
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Histological Profiling of the Human Umbilical Cord: A Potential Alternative Cell Source in Tissue Engineering. J Pers Med 2022; 12:jpm12040648. [PMID: 35455764 PMCID: PMC9028794 DOI: 10.3390/jpm12040648] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 04/05/2022] [Accepted: 04/15/2022] [Indexed: 02/01/2023] Open
Abstract
The embryonic development of the human umbilical cord (hUC) is complex, and different regions can be identified in this structure. The aim of this work is to characterize the hUC at in situ and ex vivo levels to stablish their potential use in vascular regeneration. Human umbilical cords were obtained and histologically prepared for in the situ analysis of four hUC regions (intervascular—IV, perivascular—PV, subaminoblastic—SAM, and Wharton’s jelly—WH), and primary cell cultures of mesenchymal stem cells (hUC-MSC) isolated from each region were obtained. The results confirmed the heterogeneity of the hUC, with the IV and PV zones tending to show the higher in situ expression of several components of the extracellular matrix (collagens, proteoglycans, and glycosaminoglycans), vimentin, and MSC markers (especially CD73), although isolation and ex vivo culture resulted in a homogeneous cell profile. Three vascular markers were positive in situ, especially vWF, followed by CD34 and CD31, and isolation and culture revealed that the region associated with the highest expression of vascular markers was IV, followed by PV. These results confirm the heterogeneity of the hUC and the need for selecting cells from specific regions of the hUC for particular applications in tissue engineering.
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27
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Omar SA, Abdul-Hafez A, Ibrahim S, Pillai N, Abdulmageed M, Thiruvenkataramani RP, Mohamed T, Madhukar BV, Uhal BD. Stem-Cell Therapy for Bronchopulmonary Dysplasia (BPD) in Newborns. Cells 2022; 11:cells11081275. [PMID: 35455954 PMCID: PMC9025385 DOI: 10.3390/cells11081275] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 03/30/2022] [Accepted: 04/07/2022] [Indexed: 11/17/2022] Open
Abstract
Premature newborns are at a higher risk for the development of respiratory distress syndrome (RDS), acute lung injury (ALI) associated with lung inflammation, disruption of alveolar structure, impaired alveolar growth, lung fibrosis, impaired lung angiogenesis, and development of bronchopulmonary dysplasia (BPD) with severe long-term developmental adverse effects. The current therapy for BPD is limited to supportive care including high-oxygen therapy and pharmacotherapy. Recognizing more feasible treatment options to improve lung health and reduce complications associated with BPD is essential for improving the overall quality of life of premature infants. There is a reduction in the resident stem cells in lungs of premature infants with BPD, which strongly suggests a critical role of stem cells in BPD pathogenesis; this warrants the exploration of the potential therapeutic use of stem-cell therapy. Stem-cell-based therapies have shown promise for the treatment of many pathological conditions including acute lung injury and BPD. Mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (EVs) including exosomes are promising and effective therapeutic modalities for the treatment of BPD. Treatment with MSCs and EVs may help to reduce lung inflammation, improve pulmonary architecture, attenuate pulmonary fibrosis, and increase the survival rate.
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Affiliation(s)
- Said A. Omar
- Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (A.A.-H.); (S.I.); (N.P.); (M.A.); (R.P.T.); (T.M.); (B.V.M.)
- Regional Neonatal Intensive Care Unit, Sparrow Health System, Lansing, MI 48912, USA
- Correspondence: ; Tel.: +1-517-364-2948
| | - Amal Abdul-Hafez
- Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (A.A.-H.); (S.I.); (N.P.); (M.A.); (R.P.T.); (T.M.); (B.V.M.)
| | - Sherif Ibrahim
- Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (A.A.-H.); (S.I.); (N.P.); (M.A.); (R.P.T.); (T.M.); (B.V.M.)
| | - Natasha Pillai
- Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (A.A.-H.); (S.I.); (N.P.); (M.A.); (R.P.T.); (T.M.); (B.V.M.)
| | - Mohammed Abdulmageed
- Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (A.A.-H.); (S.I.); (N.P.); (M.A.); (R.P.T.); (T.M.); (B.V.M.)
- Regional Neonatal Intensive Care Unit, Sparrow Health System, Lansing, MI 48912, USA
| | - Ranga Prasanth Thiruvenkataramani
- Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (A.A.-H.); (S.I.); (N.P.); (M.A.); (R.P.T.); (T.M.); (B.V.M.)
- Regional Neonatal Intensive Care Unit, Sparrow Health System, Lansing, MI 48912, USA
| | - Tarek Mohamed
- Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (A.A.-H.); (S.I.); (N.P.); (M.A.); (R.P.T.); (T.M.); (B.V.M.)
- Regional Neonatal Intensive Care Unit, Sparrow Health System, Lansing, MI 48912, USA
| | - Burra V. Madhukar
- Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (A.A.-H.); (S.I.); (N.P.); (M.A.); (R.P.T.); (T.M.); (B.V.M.)
| | - Bruce D. Uhal
- Department of Physiology, Michigan State University, East Lansing, MI 48824, USA;
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Barlian A, Saputri DHA, Hernando A, Khoirinaya C, Prajatelistia E, Tanoto H. Spidroin striped micropattern promotes chondrogenic differentiation of human Wharton's jelly mesenchymal stem cells. Sci Rep 2022; 12:4837. [PMID: 35319008 PMCID: PMC8941093 DOI: 10.1038/s41598-022-08982-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 03/14/2022] [Indexed: 11/29/2022] Open
Abstract
Cartilage tissue engineering, particularly micropattern, can influence the biophysical properties of mesenchymal stem cells (MSCs) leading to chondrogenesis. In this research, human Wharton’s jelly MSCs (hWJ-MSCs) were grown on a striped micropattern containing spider silk protein (spidroin) from Argiope appensa. This research aims to direct hWJ-MSCs chondrogenesis using micropattern made of spidroin bioink as opposed to fibronectin that often used as the gold standard. Cells were cultured on striped micropattern of 500 µm and 1000 µm width sizes without chondrogenic differentiation medium for 21 days. The immunocytochemistry result showed that spidroin contains RGD sequences and facilitates cell adhesion via integrin β1. Chondrogenesis was observed through the expression of glycosaminoglycan, type II collagen, and SOX9. The result on glycosaminoglycan content proved that 1000 µm was the optimal width to support chondrogenesis. Spidroin micropattern induced significantly higher expression of SOX9 mRNA on day-21 and SOX9 protein was located inside the nucleus starting from day-7. COL2A1 mRNA of spidroin micropattern groups was downregulated on day-21 and collagen type II protein was detected starting from day-14. These results showed that spidroin micropattern enhances chondrogenic markers while maintains long-term upregulation of SOX9, and therefore has the potential as a new method for cartilage tissue engineering.
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Affiliation(s)
- Anggraini Barlian
- School of Life Sciences and Technology, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia. .,Research Center for Nanosciences and Nanotechnology, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia.
| | - Dinda Hani'ah Arum Saputri
- School of Life Sciences and Technology, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia
| | - Adriel Hernando
- School of Life Sciences and Technology, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia
| | - Candrani Khoirinaya
- School of Life Sciences and Technology, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia
| | - Ekavianty Prajatelistia
- Faculty of Mechanical and Aerospace Engineering, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia
| | - Hutomo Tanoto
- Faculty of Mechanical and Aerospace Engineering, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia
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29
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Zheng X, Gan S, Su C, Zheng Z, Liao Y, Shao J, Zhu Z, Chen W. Screening and preliminary identification of long non-coding RNAs critical for osteogenic differentiation of human umbilical cord mesenchymal stem cells. Bioengineered 2022; 13:6880-6894. [PMID: 35249446 PMCID: PMC8973756 DOI: 10.1080/21655979.2022.2044274] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Human umbilical cord mesenchymal stem cells (hUCMSCs) are attractive therapeutic cells for tissue engineering to treat bone defects. However, how the cells can differentiate into bone remains unclear. Long non-coding RNAs (lncRNAs) are non-coding RNAs that participate in many biological processes, including stem cell differentiation. In this study, we investigated the profiles and functions of lncRNAs in the osteogenic differentiation of hUCMSCs. We identified 343 lncRNAs differentially expressed during osteogenic differentiation, of which 115 were upregulated and 228 were downregulated. We further analyzed these lncRNAs using bioinformatic analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. GO and KEGG pathway analysis showed that ‘intracellular part’ and ‘Phosphatidylinositol signaling system’ were the most correlated molecular function and pathway, respectively. We selected the top 10 upregulated lncRNAs to construct six competing endogenous RNA networks. We validated the impact of the lncRNA H19 on osteogenic differentiation by overexpressing it in hUCMSCs. Overall, our results pave the way to detailed studies of the molecular mechanisms of hUCMSC osteogenic differentiation, and they provide a new theoretical basis to guide the therapeutic application of hUCMSCs.
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Affiliation(s)
- Xiao Zheng
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.,Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.,Department of Pediatric Dentistry, Shenzhen Stomatology Hospital (Pingshan), Southern Medical University, Shenzhen, Guangdong, China
| | - Shuaiqi Gan
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.,Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Cheng Su
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.,Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Zheng Zheng
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.,Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Yihan Liao
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.,Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Jingjing Shao
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.,Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Zhimin Zhu
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.,Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Wenchuan Chen
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.,Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
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30
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Liang Q, Li Q, Ren B, Yin ZQ. Intravenous infusion of small umbilical cord mesenchymal stem cells could enhance safety and delay retinal degeneration in RCS rats. BMC Ophthalmol 2022; 22:67. [PMID: 35144581 PMCID: PMC8832832 DOI: 10.1186/s12886-021-02171-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Accepted: 11/10/2021] [Indexed: 11/25/2022] Open
Abstract
Background Human umbilical cord mesenchymal stem cells (UCMSCs) transplantation is a promising therapy for the treatment of retinitis pigmentosa (RP). However, intravenously infused cells may be blocked in the lung, increasing the risk of vascular obstruction, which needs to be optimized to further improve safety and efficacy. Methods We derived small UCMSCs (S-UCMSCs) from filtering UCMSCs with a 10-μm filter, and compared with UCMSCs by flow cytometry, directional differentiation culture and transcriptome sequencing. Then the S-UCMSCs and UCMSCs were intravenously infused in the Royal College Surgeons (RCS) rats to evaluate the safety and the efficacy. Results The diameter of S-UCMSCs ranged from 5.568 to 17.231 μm, with an average diameter of 8.636 ± 2.256 μm, which was significantly smaller than that of UCMSCs. Flow cytometry, immunofluorescence and transcriptome sequencing demonstrated that the S-UCMSCs and UCMSCs were the same kind of MSCs, and the S-UCMSCs were more proliferative. After the S-UCMSCs and UCMSCs were intravenously infused into the Royal College of Surgeons (RCS) rats at a dose of 1 × 106 cells/rat, the S-UCMSCs blocked in the lungs were significantly fewer and disappeared more quickly than UCMSCs. The b wave of the flash electroretinogram was improved at 7 d, and the retinal outer nuclear layer thickness was thicker at 7 d and 14 d. The expression level of inflammation was inhibited, and the expression level of neurotrophic factors was upregulated in the retina and serum after transplantation. Conclusions S-UCMSCs intravenous infusion was safer than UCMSCs and could delay retinal degeneration and protect visual function in RCS rats, which may be a preferable therapeutic approach for RP. Supplementary Information The online version contains supplementary material available at 10.1186/s12886-021-02171-3.
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Affiliation(s)
- Qingling Liang
- Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Amy Medical University), Chongqing, 400038, China. .,Key Lab of Visual Damage and Regeneration & Restoration, Chongqing, 400038, China.
| | - Qiyou Li
- Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Amy Medical University), Chongqing, 400038, China.,Key Lab of Visual Damage and Regeneration & Restoration, Chongqing, 400038, China
| | - Bangqi Ren
- Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Amy Medical University), Chongqing, 400038, China.,Key Lab of Visual Damage and Regeneration & Restoration, Chongqing, 400038, China
| | - Zheng Qin Yin
- Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Amy Medical University), Chongqing, 400038, China. .,Key Lab of Visual Damage and Regeneration & Restoration, Chongqing, 400038, China.
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31
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Bie Q, Zhai R, Chen Y, Li Y, Xie N, Wang B, Yuan P, Zhou X, Cong H, Chang X, Xiong H, Zhang B. Sox9 Is Crucial for Mesenchymal Stem Cells to Enhance Cutaneous Wound Healing. Int J Stem Cells 2021; 14:465-474. [PMID: 34456192 PMCID: PMC8611311 DOI: 10.15283/ijsc21078] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 06/09/2021] [Accepted: 07/08/2021] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Human umbilical cord mesenchymal stem cells (HUC-MSCs) are promising candidates for cell-based therapy in regenerative medicine or other diseases due to their superior characteristics, including higher proliferation, faster self-renewal ability, lower immunogenicity, a noninvasive harvest procedure, easy expansion in vitro, and ethical access, compared with stem cells from other sources. METHODS AND RESULTS In the present study, we knocked down the expression of SOX9 in HUC-MSCs by lentivirus interference and found that knockdown of SOX9 inhibited the proliferation and migration of HUC-MSCs and influenced the expression of cytokines (IL-6 and IL-8), growth factors (GM-CSF and VEGF) and stemness-related genes (OCT4 and SALL4). In addition, the repair effect of skin with burn injury in rats treated with HUC-MSCs transfected with sh-control was better than that rats treated with HUC-MSCs transfected with shSOX9 or PBS, and the accessory structures of the skin, including hair follicles and glands, were greater than those in the other groups. We found that knockdown of the expression of SOX9 obviously inhibited the expression of Ki67, CK14 and CK18. CONCLUSIONS In conclusion, this study will provide a guide for modifying HUC-MSCs by bioengineering technology in the future.
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Affiliation(s)
- Qingli Bie
- Department of Laboratory Medicine, Affiliated Hospital of
Jining Medical University, Jining Medical University, Jining,
China
- Institute of Forensic Medicine and Laboratory Medicine,
Jining Medical University, Jining, China
| | - Ruixia Zhai
- Department of Obstetric, Affiliated Hospital of Jining
Medical University, Jining Medical University, Jining,
China
| | - Yanrong Chen
- Department of Laboratory Medicine, Affiliated Hospital of
Jining Medical University, Jining Medical University, Jining,
China
| | - Yingao Li
- Department of Laboratory Medicine, Affiliated Hospital of
Jining Medical University, Jining Medical University, Jining,
China
| | - Na Xie
- Department of Laboratory Medicine, Affiliated Hospital of
Jining Medical University, Jining Medical University, Jining,
China
| | - Baoyi Wang
- Institute of Forensic Medicine and Laboratory Medicine,
Jining Medical University, Jining, China
| | - Poyun Yuan
- Institute of Forensic Medicine and Laboratory Medicine,
Jining Medical University, Jining, China
| | - Xinjie Zhou
- Institute of Forensic Medicine and Laboratory Medicine,
Jining Medical University, Jining, China
| | - Haiyan Cong
- Department of Central Lab, Weihai Municipal Hospital,
Cheeloo College of Medicine, Weihai, China
| | - Xin Chang
- Department of Central Lab, Weihai Municipal Hospital,
Cheeloo College of Medicine, Weihai, China
| | - Huabao Xiong
- Institute of Immunology and Molecular Medicine, Jining
Medical University, Jining, China
| | - Bin Zhang
- Department of Laboratory Medicine, Affiliated Hospital of
Jining Medical University, Jining Medical University, Jining,
China
- Institute of Forensic Medicine and Laboratory Medicine,
Jining Medical University, Jining, China
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32
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Li H, Yuan F, Du Y, Pan T, Wen W, Li S, Wang L, Lu A. Umbilical cord blood stem cells transplantation in a patient with severe progressive supranuclear palsy: a case report. J Med Case Rep 2021; 15:574. [PMID: 34844635 PMCID: PMC8628425 DOI: 10.1186/s13256-021-03139-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Accepted: 10/01/2021] [Indexed: 12/05/2022] Open
Abstract
Background Progressive supranuclear palsy is a neurodegenerative condition that worsens over time. Given the lack of targeted treatments, patients with severe progressive supranuclear palsy have very low life expectancy. Case presentation We present a case of a 61-year-old Chinese man with severe progressive supranuclear palsy and treated with umbilical cord blood stem cells transplantation. After the umbilical cord blood stem cells therapy, his neurologic symptoms stopped deteriorating, his muscle rigidity was mildly improved, and he remains alive for more than 8 years. Conclusions Umbilical cord blood stem cells transplantation may be an alternative therapy for patients with severe progressive supranuclear palsy.
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Affiliation(s)
- Huiping Li
- Department of Neurocritical Care, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China
| | - Fang Yuan
- Department of Neurocritical Care, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China
| | - Yaming Du
- Department of Neurocritical Care, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China
| | - Tao Pan
- Department of Neurocritical Care, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China
| | - Wanxin Wen
- Department of Neurocritical Care, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China
| | - Shaoxue Li
- Department of Neurocritical Care, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China
| | - Lixin Wang
- Department of Neurocritical Care, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.
| | - Aili Lu
- Department of Neurocritical Care, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.
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33
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Kulus M, Sibiak R, Stefańska K, Zdun M, Wieczorkiewicz M, Piotrowska-Kempisty H, Jaśkowski JM, Bukowska D, Ratajczak K, Zabel M, Mozdziak P, Kempisty B. Mesenchymal Stem/Stromal Cells Derived from Human and Animal Perinatal Tissues-Origins, Characteristics, Signaling Pathways, and Clinical Trials. Cells 2021; 10:cells10123278. [PMID: 34943786 PMCID: PMC8699543 DOI: 10.3390/cells10123278] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/13/2021] [Accepted: 11/19/2021] [Indexed: 12/15/2022] Open
Abstract
Mesenchymal stem/stromal cells (MSCs) are currently one of the most extensively researched fields due to their promising opportunity for use in regenerative medicine. There are many sources of MSCs, of which cells of perinatal origin appear to be an invaluable pool. Compared to embryonic stem cells, they are devoid of ethical conflicts because they are derived from tissues surrounding the fetus and can be safely recovered from medical waste after delivery. Additionally, perinatal MSCs exhibit better self-renewal and differentiation properties than those derived from adult tissues. It is important to consider the anatomy of perinatal tissues and the general description of MSCs, including their isolation, differentiation, and characterization of different types of perinatal MSCs from both animals and humans (placenta, umbilical cord, amniotic fluid). Ultimately, signaling pathways are essential to consider regarding the clinical applications of MSCs. It is important to consider the origin of these cells, referring to the anatomical structure of the organs of origin, when describing the general and specific characteristics of the different types of MSCs as well as the pathways involved in differentiation.
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Affiliation(s)
- Magdalena Kulus
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (M.K.); (K.R.)
| | - Rafał Sibiak
- Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland; (R.S.); (K.S.)
- Division of Reproduction, Department of Obstetrics, Gynecology, and Gynecologic Oncology, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Katarzyna Stefańska
- Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland; (R.S.); (K.S.)
| | - Maciej Zdun
- Department of Basic and Preclinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (M.Z.); (M.W.); (H.P.-K.)
| | - Maria Wieczorkiewicz
- Department of Basic and Preclinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (M.Z.); (M.W.); (H.P.-K.)
| | - Hanna Piotrowska-Kempisty
- Department of Basic and Preclinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (M.Z.); (M.W.); (H.P.-K.)
- Department of Toxicology, Poznan University of Medical Sciences, 60-631 Poznan, Poland
| | - Jędrzej M. Jaśkowski
- Department of Diagnostics and Clinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (J.M.J.); (D.B.)
| | - Dorota Bukowska
- Department of Diagnostics and Clinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (J.M.J.); (D.B.)
| | - Kornel Ratajczak
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (M.K.); (K.R.)
| | - Maciej Zabel
- Division of Anatomy and Histology, University of Zielona Gora, 65-046 Zielona Gora, Poland;
| | - Paul Mozdziak
- Prestage Department of Poultry Science, North Carolina State University, Raleigh, NC 27695, USA;
| | - Bartosz Kempisty
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (M.K.); (K.R.)
- Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland; (R.S.); (K.S.)
- Prestage Department of Poultry Science, North Carolina State University, Raleigh, NC 27695, USA;
- Department of Anatomy, Poznan University of Medical Sciences, 60-781 Poznan, Poland
- Correspondence:
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Lo HY, Cheng SP, Huang JL, Chang KT, Chang YL, Huang CH, Chang CJ, Chiu CH, Chen-Yang YW, Chan CK. High Induction of IL-6 Secretion From hUCMSCs Optimize the Potential of hUCMSCs and TCZ as Therapy for COVID-19-Related ARDS. Cell Transplant 2021; 30:9636897211054481. [PMID: 34757857 PMCID: PMC8586187 DOI: 10.1177/09636897211054481] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Biological and cellular interleukin-6 (IL-6)-related therapies have been used to treat severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure, which prompted further exploration of the role of IL-6 in human umbilical cord mesenchymal stem cell (hUCMSC) therapy. Peripheral blood mononuclear cells (PBMCs) were responders cocultured with hUCMSCs or exogenous IL-6. A PBMC suppression assay was used to analyze the anti-inflammatory effects via MTT assay. The IL-6 concentration in the supernatant was measured using ELISA. The correlation between the anti-inflammatory effect of hUCMSCs and IL-6 levels and the relevant roles of IL-6 and IL-6 mRNA expression was analyzed using the MetaCore functional network constructed from gene microarray data. The location of IL-6 and IL-6 receptor (IL-6R) expression was further evaluated. We reported that hUCMSCs did not initially exert any inhibitory effect on PHA-stimulated proliferation; however, a potent inhibitory effect on PHA-stimulated proliferation was observed, and the IL-6 concentration reached approximately 1000 ng/mL after 72 hours. Exogenous 1000 ng/mL IL-6 inhibited PHA-stimulated inflammation but less so than hUCMSCs. The inhibitory effects of hUCMSCs on PHA-stimulated PBMCs disappeared after adding an IL-6 neutralizing antibody or pretreatment with tocilizumab (TCZ), an IL-6R antagonist. hUCMSCs exert excellent anti-inflammatory effects by inducing higher IL-6 levels, which is different from TCZ. High concentration of IL-6 cytokine secretion plays an important role in the anti-inflammatory effect of hUCMSC therapy. Initial hUCMSC therapy, followed by TCZ, seems to optimize the therapeutic potential to treat COVID-19-related acute respiratory distress syndrome (ARDS).
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Affiliation(s)
- Huei-Yu Lo
- Department of Rehabilitation, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan.,Department of Chemistry, Chung Yuan Christian University, Taoyuan.,Translational Medicine Center, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan
| | - Shun-Ping Cheng
- Department of Rehabilitation, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan.,Translational Medicine Center, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan
| | - Jing-Long Huang
- Division of Allergy, Asthma and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan
| | - Kuo-Ting Chang
- Translational Medicine Center, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan
| | - Yu-Lung Chang
- Translational Medicine Center, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan.,Department of Urology, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan.,Department of Urology, School of Medicine, National Yang-Ming University, Taipei
| | - Chien-Hsun Huang
- Department of Obstetrics & Gynecology, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan
| | - Chia-Jen Chang
- Translational Medicine Center, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan.,Department of Food Science, Fu Jen Catholic University, New Taipei City
| | - Chien-Hua Chiu
- Translational Medicine Center, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan
| | | | - Chin-Kan Chan
- Translational Medicine Center, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan.,Department of Pediatrics, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan.,Department of Biotechnology, Ming Chuan University, Taoyuan
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35
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Puah PY, Moh PY, Sipaut CS, Lee PC, How SE. Peptide Conjugate on Multilayer Graphene Oxide Film for the Osteogenic Differentiation of Human Wharton's Jelly-Derived Mesenchymal Stem Cells. Polymers (Basel) 2021; 13:3290. [PMID: 34641106 PMCID: PMC8512023 DOI: 10.3390/polym13193290] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 09/19/2021] [Accepted: 09/24/2021] [Indexed: 12/14/2022] Open
Abstract
Graphene oxide (GO) is extensively studied as a template material for mesenchymal stem cell application due to its two-dimensional nature and unique functionalization chemistries. Herein, a new type of peptide-conjugated multilayer graphene oxide (peptide/m-GO film) was fabricated and used as biomaterial for culturing human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs). The characterization of the peptide/m-GO films was performed, and the biocompatibility of the WJ-MSCs on the peptide/m-GO films was investigated. The results demonstrated that the peptide conjugate on the m-GO film did not hamper the normal growth of WJ-MSCs but supported the growth of WJ-MSCs after the 6-day culture period. In addition, the osteogenic differentiation of WJ-MSCs on the peptide/m-GO films was enhanced as compared with the parent m-GO film. Therefore, such peptide-conjugated m-GO films could provide a highly biocompatible and multifunctional 2D material to tailor the potential application of WJ-MSCs in bone tissue regeneration.
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Affiliation(s)
- Perng Yang Puah
- Programme of Biotechnology, Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu 88400, Sabah, Malaysia; (P.Y.P.); (P.C.L.)
- Programme of Industrial Chemistry, Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu 88400, Sabah, Malaysia
- Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu 88400, Sabah, Malaysia
| | - Pak Yan Moh
- Programme of Industrial Chemistry, Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu 88400, Sabah, Malaysia
| | - Coswald Stephen Sipaut
- Programme of Chemical Engineering, Faculty of Engineering, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu 88400, Sabah, Malaysia;
| | - Ping Chin Lee
- Programme of Biotechnology, Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu 88400, Sabah, Malaysia; (P.Y.P.); (P.C.L.)
- Biotechnology Research Institute, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu 88400, Sabah, Malaysia
| | - Siew Eng How
- Programme of Industrial Chemistry, Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu 88400, Sabah, Malaysia
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Gamage TKJB, Fraser M. The Role of Extracellular Vesicles in the Developing Brain: Current Perspective and Promising Source of Biomarkers and Therapy for Perinatal Brain Injury. Front Neurosci 2021; 15:744840. [PMID: 34630028 PMCID: PMC8498217 DOI: 10.3389/fnins.2021.744840] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 08/23/2021] [Indexed: 12/12/2022] Open
Abstract
This comprehensive review focuses on our current understanding of the proposed physiological and pathological functions of extracellular vesicles (EVs) in the developing brain. Furthermore, since EVs have attracted great interest as potential novel cell-free therapeutics, we discuss advances in the knowledge of stem cell- and astrocyte-derived EVs in relation to their potential for protection and repair following perinatal brain injury. This review identified 13 peer-reviewed studies evaluating the efficacy of EVs in animal models of perinatal brain injury; 12/13 utilized mesenchymal stem cell-derived EVs (MSC-EVs) and 1/13 utilized astrocyte-derived EVs. Animal model, method of EV isolation and size, route, timing, and dose administered varied between studies. Notwithstanding, EV treatment either improved and/or preserved perinatal brain structures both macroscopically and microscopically. Additionally, EV treatment modulated inflammatory responses and improved brain function. Collectively this suggests EVs can ameliorate, or repair damage associated with perinatal brain injury. These findings warrant further investigation to identify the optimal cell numbers, source, and dosage regimens of EVs, including long-term effects on functional outcomes.
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Wang R, Wang X, Yang S, Xiao Y, Jia Y, Zhong J, Gao Q, Zhang X. Umbilical cord-derived mesenchymal stem cells promote myeloid-derived suppressor cell enrichment by secreting CXCL1 to prevent graft-versus-host disease after hematopoietic stem cell transplantation. Cytotherapy 2021; 23:996-1006. [PMID: 34465514 DOI: 10.1016/j.jcyt.2021.07.009] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 07/14/2021] [Accepted: 07/15/2021] [Indexed: 12/31/2022]
Abstract
BACKGROUND AIMS Human mesenchymal stem cells (MSCs) from various tissues have emerged as attractive candidates for the prevention and treatment of graft-versus-host disease (GVHD). However, the molecular machinery that defines and channels the behavior of these cells remains poorly understood. METHODS In this study, the authors compared the efficacy of four tissue-derived MSC types in controlling GVHD in a murine model and investigated their immunomodulatory effects. RESULTS Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) effectively decreased the incidence and severity of GVHD, which was mediated by the enrichment of myeloid-derived suppressor cells in GVHD target tissues. RNA sequencing results showed that hUCMSCs highly expressed CXCL1. CONCLUSIONS These results suggest a novel prophylactic application of hUCMSCs for controlling GVHD after allogeneic hematopoietic stem cell transplantation.
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Affiliation(s)
- Rui Wang
- Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xiaoqi Wang
- Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University (Army Medical University), Chongqing, China
| | - Shijie Yang
- Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yunshuo Xiao
- Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yanhui Jia
- Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University (Army Medical University), Chongqing, China
| | - Jiangfan Zhong
- Department of Cell Biology, College of Basic Medicine, Third Military Medical University (Army Medical University), Chongqing, China
| | - Qiangguo Gao
- Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, California, USA.
| | - Xi Zhang
- Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University (Army Medical University), Chongqing, China.
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Xie Y, Chen F, Jia L, Chen R, Zhang VW, Zhong X, Wang D. Mesenchymal stem cells from different sources show distinct therapeutic effects in hyperoxia-induced bronchopulmonary dysplasia in rats. J Cell Mol Med 2021; 25:8558-8566. [PMID: 34322990 PMCID: PMC8419191 DOI: 10.1111/jcmm.16817] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 06/28/2021] [Accepted: 07/13/2021] [Indexed: 12/23/2022] Open
Abstract
Mesenchymal stem cells (MSCs) have been shown as an effective medicinal means to treat bronchopulmonary dysplasia (BPD). The widely used MSCs were from Wharton's jelly of umbilical cord (UC-MSCs) and bone marrow (BM-MSCs). Amniotic fluid MSCs (AF-MSCs) may be produced before an individual is born to treat foetal diseases by autoplastic transplantation. We evaluated intratracheal (IT) MSCs as an approach to treat an hyperoxia-induced BPD animal model and compared the therapeutic effects between AF-, UC- and BM-MSCs. A BPD animal model was generated by exposing newborn rats to 95% O2 . The continued stress lasted 21 days, and the treatment of IT MSCs was conducted for 4 days. The therapeutic effects were analysed, including lung histology, level of inflammatory cytokines, cell death ratio and state of angiogenesis, by sacrificing the experimental animal at day 21. The lasting hyperoxia stress induced BPD similar to the biological phenotype. The treatment of IT MSCs was safe without deaths and normal organ histopathology. Specifically, the treatment was effective by inhibiting the alveolar dilatation, reducing inflammatory cytokines, inducing angiogenesis and lowering the cell death ratio. AF-MSCs had better therapeutic effects compared with UC-MSCs in relieving the pulmonary alveoli histological changes and promoting neovascularization, and UC-MSCs had the best immunosuppressive effect in plasma and lung lysis compared with AF-MSCs and BM-MSCs. This study demonstrated the therapeutic effects of AF-, UC- and BM-MSCs in BPD model. Superior treatment effect was provided by antenatal MSCs compared to BM-MSC in a statistical comparison.
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Affiliation(s)
- Yingjun Xie
- Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Fei Chen
- Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Lei Jia
- Reproductive Medicine Research Center, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Rui Chen
- Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | | | - Xinqi Zhong
- Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Department of Pediatrics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Ding Wang
- Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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Yang R, Chen G, Muhashi M, Aizezi G, Jiang M, Yuan H. Adjuvant treatment with adipose-derived mesenchymal stem cells (ADSC) reduces severe refractory hemorrhagic cystitis after RIC-PBSCT: A case report. Medicine (Baltimore) 2021; 100:e26316. [PMID: 34190149 PMCID: PMC8257885 DOI: 10.1097/md.0000000000026316] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 05/25/2021] [Indexed: 01/04/2023] Open
Abstract
INTRODUCTION Severe hemorrhagic cystitis (HC) is still a common complication after allogeneic hematopoietic stem cell transplantation, which affects the quality of life of patients, and may even cause kidney failure. This study reports the clinical effect of adjuvant treatment of adipose-derived mesenchymal stem cells (ADSCs) on severe refractory HC after of reduced intensity conditioning haplotype high-dose peripheral blood hematopoietic stem cell transplantation (RIC-PBSCT) in one case. PATIENT CONCERNS A 53-year-old female patient with acute myeloid leukemia (FLT3-ITD) at high risk received RIC-PBSCT. The patient was relieved with complete donor chimerism of 99.01%, and normal hemogram. However, the patient developed frequent urination, urgency, and dysuria with gross hematuria with blood clots and difficult urinating, especially at night and early in the morning. There were obvious hyperemia and bleeding points in the mucosa of the posterior wall of the bladder. DIAGNOSIS The patient was diagnosed as delayed HC of degree IV. INTERVENTIONS AND OUTCOMES The patient was treated with antiviral drugs, urine alkalization, and diuretic drugs for more than 1 month, but no significant effect was obtained. Thus, the patient was then given ADSCs (1 × 106 kg per kg of body weight, infused once a week for a total of 3 infusions). Symptoms of frequent urination, urgency, and dysuria that happened during the first infusion were improved, and blood clots in the urine were also reduced. After the third infusion, HC symptoms disappeared, the red blood cells were normal, and there was no fever, chills, low infusion blood pressure, or rash. The patient's HC was cured. During follow-up, HC recurrence was not observed. CONCLUSION ADSCs adjuvant treatment of relapsed and refractory severe HC is safe and reliable with good clinical efficacy. It shows certain clinical application value, which however requires more clinical cases to further verify this.
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Hansen M, Stahl L, Heider A, Hilger N, Sack U, Kirschner A, Cross M, Fricke S. Reduction of Graft-versus-Host-Disease in NOD.Cg-Prkdc scid Il2rg tm1Wjl/SzJ (NSG) Mice by Cotransplantation of Syngeneic Human Umbilical Cord-Derived Mesenchymal Stromal Cells. Transplant Cell Ther 2021; 27:658.e1-658.e10. [PMID: 33964513 DOI: 10.1016/j.jtct.2021.04.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 04/16/2021] [Accepted: 04/25/2021] [Indexed: 12/12/2022]
Abstract
Graft-versus-host disease (GVHD) is one of the major complications following hematopoietic stem cell transplantation, which remains the sole curative therapy for many malignant diseases of the hematopoietic system. The immunomodulatory potential of mesenchymal stromal cells (MSCs) to treat GVHD is currently being tested in various preclinical and clinical trials. Because the results of the preclinical and clinical trials on the use of MSCs to treat GVHD have not been consistent, we analyzed the potential beneficial effects of syngeneic versus allogenic treatment, culture expansion of MSCs, and various MSC cell doses and time points of MSC transplantation in a murine GVHD model. We established the murine GVHD model based on the transplantation of umbilical cord blood-derived hematopoietic stem cells (UC-HSCs) and used this model to assess the therapeutic potential of umbilical cord blood-derived MSCs (UC-MSCs). The use of HSC and MSC populations derived from the same donor allowed us to exclude third-party cells and test the UC-HSCs and UC-MSCs in a matched setting. Moreover, we were able to compare various doses, transplantation time points, and the influence of culture expansion of MSCs on the impact of treatment. This resulted in 16 different treatment groups. The most efficient setting for treatment of UC-HSC-induced GVHD reactions was based on the simultaneous administration of 1 × 106 culture-expanded, syngeneically matched UC-MSCs. This therapy effectively reduced the number of CD8+ T cells in the blood, protected the mice from weight loss, and prolonged their survival until the end of observation period. Taken together, our data show beneficial effects of (1) syngeneic over allogeneic UC-HSCs and UC-MSCs, (2) culture-expanded cells over freshly isolated primary cells, (3) simultaneous over sequential administration, and (4) high doses of UC-MSCs. The animal model of GVHD established here is now available for more detailed studies, including a comparative analysis of the efficacy of MSCs derived from alternative sources, such as adipose tissue and bone marrow.
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Affiliation(s)
- Max Hansen
- Vita 34 AG, Leipzig, Germany; Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Leipzig, Germany.
| | - Lilly Stahl
- Tcell Tolerance GmbH, Leipzig, Germany; Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | | | - Nadja Hilger
- Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | - Ulrich Sack
- Department of Hematology and Cell Therapy, Leipzig University Hospital, Leipzig, Germany
| | - Andreas Kirschner
- Vita 34 AG, Leipzig, Germany; Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | - Michael Cross
- Department of Hematology and Cell Therapy, Leipzig University Hospital, Leipzig, Germany
| | - Stephan Fricke
- Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
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Widowati W, Murti H, Widyastuti H, Laksmitawati DR, Rizal R, Widya Kusuma HS, Sumitro SB, Widodo MA, Bachtiar I. Decreased Inhibition of Proliferation and Induction of Apoptosis in Breast Cancer Cell Lines (T47D and MCF7) from Treatment with Conditioned Medium Derived from Hypoxia-Treated Wharton's Jelly MSCs Compared with Normoxia-Treated MSCs. Int J Hematol Oncol Stem Cell Res 2021; 15:77-89. [PMID: 34466206 PMCID: PMC8381107 DOI: 10.18502/ijhoscr.v15i2.6038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Accepted: 12/15/2020] [Indexed: 11/24/2022] Open
Abstract
Background: Mesenchymal stem cells (MSCs) are an appealing source of adult stem cells for cell therapy due to the high rate of proliferation, self-renewal capability, and applicable therapy. Wharton’s jelly (WJ), the main component of the umbilical cord extracellular matrix, comprises multipotent stem cells with a high proliferation rate and self-renewal capability and has anti-cancer properties. MSCs have been reported to secrete a variety of cytokines that have a cytotoxic effect in various cancers. Oxygen tension affects MSCs proliferation, cytokines level but no in surface markers expression, MSCs’ differentiation. We explored the cytotoxic effect and inducing apoptosis of Wharton’s jelly derived mesenchymal stem cells (WJMSCs) secretions from normoxic WJMSCs (WJMSCs-norCM) (CM: conditioned medium) and hypoxic WJMSCs (WJMSCs-hypoCM) in breast cancer cell lines (T47D and MCF7). Materials and Methods: Cytotoxic activity was determined using the MTS assay. RT-PCR was performed to measure the expression of apoptosis-inducing genes, specifically P53, BAX, and CASP9, and the antiapoptotic gene BCL-2. Results: WJMSCs-norCM and WJMSCs-hypoCM were potent inhibitors of the proliferation in both cell lines. WJMSCs-norCM had more anticancer activity in T47D and MCF7. The IC50 value of WJMSCs-norCM on MCF7 was 42.34%, and on T47D was 42.36%. WJMSCs-norCM significantly induced the gene expression of apoptotic P53, BAX, and CASP9 and insignificantly decreased the antiapoptotic gene BCL-2 in both MCF7 and T47D cells. WJMSCs-CM has anticancer activity by inducing P53, BAX, and CASP9 apoptotic genes. Conclusion: WJMSCs-norCM has more anticancer activity than WJMSCs-hypoCM.
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Affiliation(s)
- Wahyu Widowati
- Faculty of Medicine, Maranatha Christian University, Jl. Prof. drg.. Suria Sumantri No.65, Bandung 40164, Indonesia
| | - Harry Murti
- Stem Cell and Cancer Institute, Jl. A Yani No 2 Pulo Mas, Jakarta 13210, Indonesia
| | - Halida Widyastuti
- Stem Cell and Cancer Institute, Jl. A Yani No 2 Pulo Mas, Jakarta 13210, Indonesia
| | - Dian Ratih Laksmitawati
- Faculty of Pharmacy, Pancasila University, Jl. Raya Lenteng Agung No.56-80 Jakarta 12640, Indonesia
| | - Rizal Rizal
- Biomolecular and Biomedical Research Center, Aretha Medika Utama,, Jl. Babakan Jeruk II No. 9, Bandung 40163, Indonesia.,Biomedical Engineering, Department of Electrical Engineering, Faculty of Engineering, Universitas Indonesia, Jl. Kampus UI, Depok 16426, West Java, Indonesia
| | - Hanna Sari Widya Kusuma
- Biomolecular and Biomedical Research Center, Aretha Medika Utama,, Jl. Babakan Jeruk II No. 9, Bandung 40163, Indonesia
| | - Sutiman Bambang Sumitro
- Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Jl. Veteran, Ketawanggede Malang 65145, Indonesia
| | - M Aris Widodo
- Pharmacology Laboratories, Faculty of Medicine, Brawijaya University Jl. Veteran, Ketawanggede Malang 65145,, Indonesia
| | - Indra Bachtiar
- Stem Cell and Cancer Institute, Jl. A Yani No 2 Pulo Mas, Jakarta 13210, Indonesia
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Shim J, Kim K, Kim KG, Choi U, Kyung JW, Sohn S, Lim SH, Choi H, Ahn T, Choi HJ, Shin D, Han I. Safety and efficacy of Wharton's jelly-derived mesenchymal stem cells with teriparatide for osteoporotic vertebral fractures: A phase I/IIa study. Stem Cells Transl Med 2021; 10:554-567. [PMID: 33326694 PMCID: PMC7980202 DOI: 10.1002/sctm.20-0308] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 10/28/2020] [Accepted: 11/17/2020] [Indexed: 12/20/2022] Open
Abstract
Osteoporotic vertebral compression fractures (OVCFs) are serious health problems. We conducted a randomized, open-label, phase I/IIa study to determine the feasibility, safety, and effectiveness of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) and teriparatide (parathyroid hormone 1-34) in OVCFs. Twenty subjects with recent OVCFs were randomized to teriparatide (20 μg/day, daily subcutaneous injection for 6 months) treatment alone or combined treatment of WJ-MSCs (intramedullary [4 × 107 cells] injection and intravenous [2 × 108 cells] injection after 1 week) and teriparatide (20 μg/day, daily subcutaneous injection for 6 months). Fourteen subjects (teriparatide alone, n = 7; combined treatment, n = 7) completed follow-up assessment (visual analog scale [VAS], Oswestry Disability Index [ODI], Short Form-36 [SF-36], bone mineral density [BMD], bone turnover measured by osteocalcin and C-terminal telopeptide of type 1 collagen, dual-energy x-ray absorptiometry [DXA], computed tomography [CT]). Our results show that (a) combined treatment with WJ-MSCs and teriparatide is feasible and tolerable for the patients with OVCFs; (b) the mean VAS, ODI, and SF-36 scores significantly improved in the combined treatment group; (c) the level of bone turnover markers were not significantly different between the two groups; (d) BMD T-scores of spine and hip by DXA increased in both control and experimental groups without a statistical difference; and (e) baseline spine CT images and follow-up CT images at 6 and 12 months showed better microarchitecture in the combined treatment group. Our results indicate that combined treatment of WJ-MSCs and teriparatide is feasible and tolerable and has a clinical benefit for fracture healing by promoting bone architecture. Clinical trial registration: https://nedrug.mfds.go.kr/, MFDS: 201600282-30937.
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Affiliation(s)
- JeongHyun Shim
- Department of NeurosurgeryShim Jeong HospitalSeoulSouth Korea
| | - Kyoung‐Tae Kim
- Department of Neurosurgery, School of MedicineKyungpook National UniversityDaeguSouth Korea
- Department of NeurosurgeryKyungpook National University HospitalDaeguSouth Korea
| | - Kwang Gi Kim
- Department of Biomedical Engineering, College of MedicineGachon UniversitySeongnam‐siSouth Korea
- Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences and Technology (GAIHST)Gachon UniversitySeongnam‐siSouth Korea
| | - Un‐Yong Choi
- Department of NeurosurgeryCHA University School of Medicine, CHA Bundang Medical CenterSeongnam‐siSouth Korea
| | - Jae Won Kyung
- Department of NeurosurgeryCHA University School of Medicine, CHA Bundang Medical CenterSeongnam‐siSouth Korea
| | - Seil Sohn
- Department of NeurosurgeryCHA University School of Medicine, CHA Bundang Medical CenterSeongnam‐siSouth Korea
| | - Sang Heon Lim
- Department of Biomedical Engineering, College of MedicineGachon UniversitySeongnam‐siSouth Korea
| | - Hyemin Choi
- Department of NeurosurgeryCHA University School of Medicine, CHA Bundang Medical CenterSeongnam‐siSouth Korea
| | - Tae‐Keun Ahn
- Department of Orthopedic SurgeryCHA University School of Medicine, CHA Bundang Medical CenterSeongnam‐siSouth Korea
| | - Hye Jeong Choi
- Department of RadiologyCHA University School of Medicine, CHA Bundang Medical CenterSeongnam‐siSouth Korea
| | - Dong‐Eun Shin
- Department of Orthopedic SurgeryCHA University School of Medicine, CHA Bundang Medical CenterSeongnam‐siSouth Korea
| | - Inbo Han
- Department of NeurosurgeryCHA University School of Medicine, CHA Bundang Medical CenterSeongnam‐siSouth Korea
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Mankuzhy PD, Ramesh ST, Thirupathi Y, Mohandas PS, Chandra V, Sharma TG. The preclinical and clinical implications of fetal adnexa derived mesenchymal stromal cells in wound healing therapy. Wound Repair Regen 2021; 29:347-369. [PMID: 33721373 DOI: 10.1111/wrr.12911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 12/06/2020] [Accepted: 03/01/2021] [Indexed: 11/28/2022]
Abstract
Mesenchymal stromal cells (MSCs) isolated from fetal adnexa namely amniotic membrane/epithelium, amniotic fluid and umbilical cord have hogged the limelight in recent times, as a proposed alternative to MSCs from conventional sources. These cells which are identified as being in a developmentally primitive state have many advantages, the most important being the non-invasive nature of their isolation procedures, absence of ethical concerns, proliferation potential, differentiation abilities and low immunogenicity. In the present review, we are focusing on the potential preclinical and clinical applications of different cell types of fetal adnexa, in wound healing therapy. We also discuss the isolation-culture methods, cell surface marker expression, multi-lineage differentiation abilities, immune-modulatory capabilities and their homing property. Different mechanisms involved in the wound healing process and the role of stromal cells in therapeutic wound healing are highlighted. Further, we summarize the findings of the cell delivery systems in skin lesion models and paracrine functions of their secretome in the wound healing process. Overall, this holistic review outlines the research findings of fetal adnexa derived MSCs, their usefulness in wound healing therapy in human as well as in veterinary medicine.
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Affiliation(s)
- Pratheesh D Mankuzhy
- Department of Physiology, Kerala Veterinary and Animal Sciences University, Pookode, Wayanad, Kerala, India
| | - Sreekumar T Ramesh
- Department of Physiology, Kerala Veterinary and Animal Sciences University, Pookode, Wayanad, Kerala, India
| | - Yasotha Thirupathi
- Physiology & Climatology Division, ICAR-Indian Veterinary Research Institute (Deemed University), Izatnagar, Uttar Pradesh, India
| | - Ponny S Mohandas
- Consultant Gynecologist, Department of Gynecology and Obstetrics, Meditrina Hospital, Ayathil, Kollam, Kerala, India
| | - Vikash Chandra
- Physiology & Climatology Division, ICAR-Indian Veterinary Research Institute (Deemed University), Izatnagar, Uttar Pradesh, India
| | - Taru Guttula Sharma
- Physiology & Climatology Division, ICAR-Indian Veterinary Research Institute (Deemed University), Izatnagar, Uttar Pradesh, India
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Qi Y, Li B, Wen Y, Yang X, Chen B, He Z, Zhao Z, Magdalou J, Wang H, Chen L. H3K9ac of TGFβRI in human umbilical cord: a potential biomarker for evaluating cartilage differentiation and susceptibility to osteoarthritis via a two-step strategy. Stem Cell Res Ther 2021; 12:163. [PMID: 33663609 PMCID: PMC7934528 DOI: 10.1186/s13287-021-02234-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 02/15/2021] [Indexed: 11/10/2022] Open
Abstract
Background Epidemiological investigation and our previous reports indicated that osteoarthritis had a fetal origin and was closely associated with intrauterine growth retardation (IUGR). Human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) could be programmable to “remember” early-life stimuli. Here, we aimed to explore an early-warning biomarker of fetal-originated adult osteoarthritis in the WJ-MSCs. Methods Firstly, two kinds of WJ-MSCs were applied to evaluate their chondrogenic potential in vitro through inducing chondrogenic differentiation as the first step of our strategy, one from newborns with IUGR and the other from normal newborns but treated with excessive cortisol during differentiation to simulate the excessive maternal glucocorticoid in the IUGR newborns. As for the second step of the strategy, the differentiated WJ-MSCs were treated with interleukin 1β (IL-1β) to mimic the susceptibility to osteoarthritis. Then, the expression and histone acetylation levels of transforming growth factor β (TGFβ) signaling pathway and the expression of histone deacetylases (HDACs) were quantified, with or without cortisol receptor inhibitor RU486, or HDAC4 inhibitor LMK235. Secondly, the histone acetylation and expression levels of TGFβRI were further detected in rat cartilage and human umbilical cord from IUGR individuals. Results Glycosaminoglycan content and the expression levels of chondrogenic genes were decreased in the WJ-MSCs from IUGR, and the expression levels of chondrogenic genes were further reduced after IL-1β treatment, while the expression levels of catabolic factors were increased. Then, serum cortisol level from IUGR individuals was found increased, and similar changes were observed in normal WJ-MSCs treated with excessive cortisol. Moreover, the decreased histone 3 lysine 9 acetylation (H3K9ac) level of TGFβRI and its expression were observed in IUGR-derived WJ-MSCs and normal WJ-MSCs treated with excessive cortisol, which could be abolished by RU486 and LMK235. At last, the decreased H3K9ac level of TGFβRI and its expression were further confirmed in the cartilage of IUGR rat offspring and human umbilical cords from IUGR newborn. Conclusions WJ-MSCs from IUGR individuals displayed a poor capacity of chondrogenic differentiation and an increased susceptibility to osteoarthritis-like phenotype, which was attributed to the decreased H3K9ac level of TGFβRI and its expression induced by high cortisol through GR/HDAC4. The H3K9ac of TGFβRI in human umbilical cord could be a potential early-warning biomarker for predicting neonatal cartilage dysplasia and osteoarthritis susceptibility. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-021-02234-8.
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Affiliation(s)
- Yongjian Qi
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.,Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China
| | - Bin Li
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.,Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China
| | - Yinxian Wen
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.,Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China
| | - Xu Yang
- Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China
| | - Biao Chen
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.,Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China
| | - Zheng He
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.,Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China
| | - Zhe Zhao
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Jacques Magdalou
- UMR 7561 CNRS-Université de Lorraine, Faculté de Médicine, Vandoeuvre-lès-Nancy, France
| | - Hui Wang
- Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. .,Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, China.
| | - Liaobin Chen
- Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. .,Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, China.
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Podestà MA, Remuzzi G, Casiraghi F. Mesenchymal Stromal Cell Therapy in Solid Organ Transplantation. Front Immunol 2021; 11:618243. [PMID: 33643298 PMCID: PMC7902912 DOI: 10.3389/fimmu.2020.618243] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 12/29/2020] [Indexed: 12/29/2022] Open
Abstract
Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored immunosuppressive agents has improved graft and patient survival remarkably in early post-transplant stages, but long-term outcomes are frequently unsatisfactory due to the development of chronic graft rejection, which ultimately leads to transplant failure. Moreover, prolonged immunosuppression entails severe side effects that severely impact patient survival and quality of life. The achievement of tolerance, i.e., stable graft function without the need for immunosuppression, is considered the Holy Grail of the field of solid organ transplantation. However, spontaneous tolerance in solid allograft recipients is a rare and unpredictable event. Several strategies that include peri-transplant administration of non-hematopoietic immunomodulatory cells can safely and effectively induce tolerance in pre-clinical models of solid organ transplantation. Mesenchymal stromal cells (MSC), non-hematopoietic cells that can be obtained from several adult and fetal tissues, are among the most promising candidates. In this review, we will focus on current pre-clinical evidence of the immunomodulatory effect of MSC in solid organ transplantation, and discuss the available evidence of their safety and efficacy in clinical trials.
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Affiliation(s)
| | - Giuseppe Remuzzi
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Aldo & Cele Daccò Clinical Research Center for Rare Diseases, Bergamo, Italy
| | - Federica Casiraghi
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Aldo & Cele Daccò Clinical Research Center for Rare Diseases, Bergamo, Italy
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Periera-Simon S, Xia X, Catanuto P, Coronado R, Kurtzberg J, Bellio M, Lee YS, Khan A, Smith R, Elliot SJ, Glassberg MK. Anti-fibrotic effects of different sources of MSC in bleomycin-induced lung fibrosis in C57BL6 male mice. Respirology 2021; 26:161-170. [PMID: 32851725 DOI: 10.1111/resp.13928] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 07/14/2020] [Accepted: 07/20/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND OBJECTIVE IPF is a fatal and debilitating lung disorder increasing in incidence worldwide. To date, two approved treatments only slow disease progression, have multiple side effects and do not provide a cure. MSC have promising therapeutic potential as a cell-based therapy for many lung disorders based on the anti-fibrotic properties of the MSC. METHODS Critical questions remain surrounding the optimal source, timing and efficacy of cell-based therapies. The present study examines the most effective sources of MSC. Human MSC were derived from adipose, WJ, chorionic membrane (CSC) and chorionic villi (CVC). MSC were injected into the ageing mouse model of BLM-induced lung fibrosis. RESULTS All sources decreased Aschroft and hydroxyproline levels when injected into BLM-treated mice at day 10 with the exception of CSC cells that did not change hydroxyproline levels. There were also decreases in mRNA expression of αv -integrin and TNFα in all sources except CSC. Only ASC- and WJ-derived cells reduced AKT and MMP-2 activation, while Cav-1 was increased by ASC treatment as previously reported. BLM-induced miR dysregulation of miR-29 and miR-199 was restored only by ASC treatment. CONCLUSION Our data suggest that sources of MSC may differ in the pathway(s) involved in repair.
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Affiliation(s)
- Simone Periera-Simon
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Xiaomei Xia
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Paola Catanuto
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
| | | | - Joanne Kurtzberg
- Marcus Center for Cellular Cures at Duke, Duke University School of Medicine, Durham, NC, USA
| | - Michael Bellio
- Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Yee-Shuan Lee
- Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Aisha Khan
- Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Robin Smith
- Department of Medicine, Rutgers University, New Brunswick, NJ, USA
| | - Sharon J Elliot
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Marilyn K Glassberg
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
- Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, The University of Arizona School of Medicine, Phoenix, AZ, USA
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de la Torre P, Flores AI. Current Status and Future Prospects of Perinatal Stem Cells. Genes (Basel) 2020; 12:6. [PMID: 33374593 PMCID: PMC7822425 DOI: 10.3390/genes12010006] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 12/18/2020] [Accepted: 12/20/2020] [Indexed: 02/05/2023] Open
Abstract
The placenta is a temporary organ that is discarded after birth and is one of the most promising sources of various cells and tissues for use in regenerative medicine and tissue engineering, both in experimental and clinical settings. The placenta has unique, intrinsic features because it plays many roles during gestation: it is formed by cells from two individuals (mother and fetus), contributes to the development and growth of an allogeneic fetus, and has two independent and interacting circulatory systems. Different stem and progenitor cell types can be isolated from the different perinatal tissues making them particularly interesting candidates for use in cell therapy and regenerative medicine. The primary source of perinatal stem cells is cord blood. Cord blood has been a well-known source of hematopoietic stem/progenitor cells since 1974. Biobanked cord blood has been used to treat different hematological and immunological disorders for over 30 years. Other perinatal tissues that are routinely discarded as medical waste contain non-hematopoietic cells with potential therapeutic value. Indeed, in advanced perinatal cell therapy trials, mesenchymal stromal cells are the most commonly used. Here, we review one by one the different perinatal tissues and the different perinatal stem cells isolated with their phenotypical characteristics and the preclinical uses of these cells in numerous pathologies. An overview of clinical applications of perinatal derived cells is also described with special emphasis on the clinical trials being carried out to treat COVID19 pneumonia. Furthermore, we describe the use of new technologies in the field of perinatal stem cells and the future directions and challenges of this fascinating and rapidly progressing field of perinatal cells and regenerative medicine.
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Affiliation(s)
| | - Ana I. Flores
- Grupo de Medicina Regenerativa, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Avda. Cordoba s/n, 28041 Madrid, Spain;
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Martínez-Aguilar R, Romero-Pinedo S, Ruiz-Magaña MJ, Olivares EG, Ruiz-Ruiz C, Abadía-Molina AC. Menstrual blood-derived stromal cells modulate functional properties of mouse and human macrophages. Sci Rep 2020; 10:21389. [PMID: 33288796 PMCID: PMC7721726 DOI: 10.1038/s41598-020-78423-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 11/24/2020] [Indexed: 12/24/2022] Open
Abstract
Menstrual blood-derived stromal cells (MenSCs) are emerging as a strong candidate for cell-based therapies due to their immunomodulatory properties. However, their direct impact on innate immune populations remains elusive. Since macrophages play a key role in the onset and development of inflammation, understanding MenSCs implication in the functional properties of these cells is required to refine their clinical effects during the treatment of inflammatory disorders. In this study, we assessed the effects that MenSCs had on the recruitment of macrophages and other innate immune cells in two mouse models of acute inflammation, a thioglycollate (TGC)-elicited peritonitis model and a monobacterial sepsis model. We found that, in the TGC model, MenSCs injection reduced the percentage of macrophages recruited to the peritoneum and promoted the generation of peritoneal immune cell aggregates. In the sepsis model, MenSCs exacerbated infection by diminishing the recruitment of macrophages and neutrophils to the site of infection and inducing defective bacterial clearance. Additional in vitro studies confirmed that co-culture with MenSCs impaired macrophage bactericidal properties, affecting bacterial killing and the production of reactive oxygen intermediates. Our findings suggest that MenSCs modulate the macrophage population and that this modulation must be taken into consideration when it comes to future clinical applications.
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Affiliation(s)
| | | | - M José Ruiz-Magaña
- Unidad de Inmunología, IBIMER, CIBM, Universidad de Granada, Granada, Spain
| | - Enrique G Olivares
- Departamento de Bioquímica y Biología Molecular III e Inmunología, Facultad de Medicina, Universidad de Granada, Granada, Spain.,Unidad de Gestión Clínica Laboratorios, Hospital Universitario Clínico San Cecilio, Granada, Spain
| | - Carmen Ruiz-Ruiz
- Unidad de Inmunología, IBIMER, CIBM, Universidad de Granada, Granada, Spain. .,Departamento de Bioquímica y Biología Molecular III e Inmunología, Facultad de Medicina, Universidad de Granada, Granada, Spain.
| | - Ana C Abadía-Molina
- Unidad de Inmunología, IBIMER, CIBM, Universidad de Granada, Granada, Spain. .,Departamento de Bioquímica y Biología Molecular III e Inmunología, Facultad de Medicina, Universidad de Granada, Granada, Spain.
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Barlian A, Judawisastra H, Ridwan A, Wahyuni AR, Lingga ME. Chondrogenic differentiation of Wharton's Jelly mesenchymal stem cells on silk spidroin-fibroin mix scaffold supplemented with L-ascorbic acid and platelet rich plasma. Sci Rep 2020; 10:19449. [PMID: 33173146 PMCID: PMC7656266 DOI: 10.1038/s41598-020-76466-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 10/21/2020] [Indexed: 01/08/2023] Open
Abstract
In this research, hWJ-MSCs were grown on silk scaffolds and induced towards chondrogenesis by supplementation with L-ascorbic acid (LAA) or platelet rich plasma (PRP). Silk scaffolds were fabricated with salt leaching method by mixing silk fibroin (SF) with silk spidroin (SS). The silk fibroin was obtained from Bombyx mori cocoon that had been degummed, and the silk spidroin was obtained from wild-type spider Argiope appensa. The effect of scaffold composition and inducer on cell proliferation was observed through MTT assay. The most optimal treatment then continued to be used to induce hWJ-MSC towards chondrogenic differentiation for 7 and 21 days. Scaffolds characterization showed that the scaffolds produced had 3D structure with interconnected pores, and all were biocompatible with hWJ-MSCs. Scaffold with the addition of 10% SS + 90% SF showed higher compressive strength and better pore interconnectivity in comparison to 100% silk fibroin scaffold. After 48 h, cells seeded on scaffold with spidroin and fibroin mix had flattened morphology in comparison to silk fibroin scaffold which appeared to be more rounded on the scaffold surface. Scaffold with 10% (w/w) of silk spidroin (SS) + 90% (w/w) of silk fibroin (SF) was the most optimal composition for cell proliferation. Immunocytochemistry of integrin β1 and RGD sequence, showed that scaffold with SS 10% provide better cell attachment with the presence of RGD sequence from the spidroin silk which could explain the higher cell proliferation than SF100% scaffold. Based on Alcian Blue staining and Collagen Type II immunocytochemistry (ICC), cells grown on 10% SS + 90% SF scaffold with 10% PRP supplementation were the most optimal to support chondrogenesis of hWJ-MSCs. These results showed that the addition of spidroin silk from A. appensa. had impact on scaffold compressive strength and chondrogenic differentiation of hWJ-MSC and had the potential for further development of bio-based material scaffold in cartilage tissue engineering.
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Affiliation(s)
- Anggraini Barlian
- School of Life Science and Technology, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia.
- Research Center for Nanosciences and Nanotechnology, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia.
| | - Hermawan Judawisastra
- Faculty of Mechanical and Aerospace Engineering, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia
| | - Ahmad Ridwan
- School of Life Science and Technology, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia
| | - Antonia Ratih Wahyuni
- School of Life Science and Technology, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia
| | - Meidiana Ebtayani Lingga
- School of Life Science and Technology, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia
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Han F, Lu P. Introduction for Stem Cell-Based Therapy for Neurodegenerative Diseases. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1266:1-8. [PMID: 33105491 DOI: 10.1007/978-981-15-4370-8_1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Neurodegenerative diseases (NDs) are a group of neurological diseases caused by the progressive degeneration of neurons and glial cells in the brain and spinal cords. Usually there is a selective loss of specific neuronal cells in a restricted brain area from any neurodegenerative diseases, such as dopamine (DA) neuron death in Parkinson disease (PD) and motor neuron loss in amyotrophic lateral sclerosis (ALS), or a widespread degeneration affecting many types of neurons in Alzheimer's disease (AD). As there is no effective treatment to stop the progression of these neurodegenerative diseases, stem cell-based therapies have provided great potentials for these disorders. Currently transplantation of different stem cells or their derivatives has improved neural function in animal models of neurodegenerative diseases by replacing the lost neural cells, releasing cytokines, modulation of inflammation, and mediating remyelination. With the advance in somatic cell reprogramming to generate induced pluripotent stem cells (iPS cells) and directly induced neural stem cells or neurons, pluripotent stem cell can be induced to differentiate to any kind of neural cells and overcome the immune rejection of the allogeneic transplantation. Recent studies have proved the effectiveness of transplanted stem cells in animal studies and some clinical trials on patients with NDs. However, some significant hurdles need to be resolved before these preclinical results can be translated to clinic. In particular, we need to better understand the molecular mechanisms of stem cell transplantation and develop new approaches to increase the directed neural differentiation, migration, survival, and functional connections of transplanted stem cells in the pathological environment of the patient's central nerve system.
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Affiliation(s)
- Fabin Han
- The Institute for Translational Medicine, Shandong University/Affiliated Second Hospital, Jinan, Shandong, China. .,The Institute for Tissue Engineering and Regenerative Medicine, Liaocheng University/Liaocheng People's Hospital, Liaocheng, Shandong, China.
| | - Paul Lu
- Veterans Administration San Diego Healthcare System, San Diego, CA, USA.,Department of Neurosciences, University of California - San Diego, La Jolla, CA, USA
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