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Xu Z, Geng J, Liu X, Zhao Z, Suo D, Zhang S, Zhong J, Suo G. The extracellular matrix with a continuous gradient of SDF1 αguides the oriented migration of human umbilical cord mesenchymal stem cells. Biomed Mater 2024; 19:065019. [PMID: 39312941 DOI: 10.1088/1748-605x/ad7e91] [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: 10/31/2023] [Accepted: 09/23/2024] [Indexed: 09/25/2024]
Abstract
The extracellular matrix (ECM) plays a crucial role in maintaining cell morphology and facilitating intercellular signal transmission within the human body. ECM has been extensively utilized for tissue injury repair. However, the consideration of factor gradients during ECM preparation has been limited. In this study, we developed a novel approach to generate sheet-like ECM with a continuous gradient of stromal cell-derived factor-1 (SDF1α). Briefly, we constructed fibroblasts to overexpress SDF1αfused with the collagen-binding domain (CBD-SDF1α), and cultured these cells on a slanted plate to establish a gradual density cell layer at the bottom surface. Subsequently, excess parental fibroblasts were evenly distributed on the plate laid flat to fill the room between cells. Following two weeks of culture, the monolayer cells were lyophilized to form a uniform ECM sheet possessing a continuous gradient of SDF1α. This engineered ECM material demonstrated its ability to guide oriented migration of human umbilical cord mesenchymal stem cells on the ECM sheet. Our simple yet effective method holds great potential for advancing research in regenerative medicine.
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Affiliation(s)
- Zhongjuan Xu
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, People's Republic of China
- Guangdong Institute of Semiconductor Micro-Nano Manufacturing Technology, Foshan 528000, People's Republic of China
| | - Junsa Geng
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, People's Republic of China
| | - Xingzhi Liu
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, People's Republic of China
| | - Zhe Zhao
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, People's Republic of China
| | - Dylan Suo
- Westlake High School, Austin, TX 78746, United States of America
| | - Sheng Zhang
- Center for Clinical Laboratory, The First Affiliated Hospital of Soochow University, Suzhou 215006, People's Republic of China
| | - Junjie Zhong
- Department of Neurosurgery, National Center for Neurological Disorders, National KeyLaboratory for Medical Neurobiology, Shanghai Key Laboratory of Brain Function and Regeneration, Institutes of Brain Science, MOE Frontiers Center for Brain Science, Fudan University Huashan Hospital, Shanghai Medical College-Fudan University, Shanghai 200040, People's Republic of China
| | - Guangli Suo
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, People's Republic of China
- Division of Nanomaterials, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Nanchang 330200, People's Republic of China
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Perocheau D, Gurung S, Touramanidou L, Duff C, Sharma G, Sebire N, Finn PF, Cavedon A, Siddiqui S, Rice L, Martini PG, Frassetto A, Baruteau J. Ex vivo precision-cut liver slices model disease phenotype and monitor therapeutic response for liver monogenic diseases. F1000Res 2024; 12:1580. [PMID: 38618017 PMCID: PMC11016166 DOI: 10.12688/f1000research.142014.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/03/2024] [Indexed: 04/16/2024] Open
Abstract
Background In academic research and the pharmaceutical industry, in vitro cell lines and in vivo animal models are considered as gold standards in modelling diseases and assessing therapeutic efficacy. However, both models have intrinsic limitations, whilst the use of precision-cut tissue slices can bridge the gap between these mainstream models. Precision-cut tissue slices combine the advantage of high reproducibility, studying all cell sub-types whilst preserving the tissue matrix and extracellular architecture, thereby closely mimicking a mini-organ. This approach can be used to replicate the biological phenotype of liver monogenic diseases using mouse models. Methods Here, we describe an optimised and easy-to-implement protocol for the culture of sections from mouse livers, enabling its use as a reliable ex-vivo model to assess the therapeutic screening of inherited metabolic diseases. Results We show that precision-cut liver sections can be a reliable model for recapitulating the biological phenotype of inherited metabolic diseases, exemplified by common urea cycle defects such as citrullinemia type 1 and argininosuccinic aciduria, caused by argininosuccinic synthase (ASS1) and argininosuccinic lyase (ASL) deficiencies respectively. Conclusions Therapeutic response to gene therapy such as messenger RNA replacement delivered via lipid nanoparticles can be monitored, demonstrating that precision-cut liver sections can be used as a preclinical screening tool to assess therapeutic response and toxicity in monogenic liver diseases.
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Affiliation(s)
- Dany Perocheau
- Great Ormond Street Institute of Child Health, University College London, London, England, WC1N 1EH, UK
| | - Sonam Gurung
- Great Ormond Street Institute of Child Health, University College London, London, England, WC1N 1EH, UK
| | - Loukia Touramanidou
- Great Ormond Street Institute of Child Health, University College London, London, England, WC1N 1EH, UK
| | - Claire Duff
- Great Ormond Street Institute of Child Health, University College London, London, England, WC1N 1EH, UK
| | - Garima Sharma
- Great Ormond Street Institute of Child Health, University College London, London, England, WC1N 1EH, UK
| | - Neil Sebire
- Great Ormond Street Hospital for Children NHS Foundation Trust, London, England, WC1N 3JH, UK
| | | | | | | | - Lisa Rice
- Moderna Inc., Cambridge, MA 02139, USA
| | | | | | - Julien Baruteau
- Great Ormond Street Institute of Child Health, University College London, London, England, WC1N 1EH, UK
- Great Ormond Street Hospital for Children NHS Foundation Trust, London, England, WC1N 3JH, UK
- National Institute of Health Research, Great Ormond Street Biomedical Research Centre, London, WC1N 1EH, UK
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Alt EU, Schmitz C, Bai X. Perspective: Why and How Ubiquitously Distributed, Vascular-Associated, Pluripotent Stem Cells in the Adult Body (vaPS Cells) Are the Next Generation of Medicine. Cells 2021; 10:2303. [PMID: 34571951 PMCID: PMC8467324 DOI: 10.3390/cells10092303] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2021] [Revised: 08/30/2021] [Accepted: 08/31/2021] [Indexed: 12/21/2022] Open
Abstract
A certain cell type can be isolated from different organs in the adult body that can differentiate into ectoderm, mesoderm, and endoderm, providing significant support for the existence of a certain type of small, vascular-associated, pluripotent stem cell ubiquitously distributed in all organs in the adult body (vaPS cells). These vaPS cells fundamentally differ from embryonic stem cells and induced pluripotent stem cells in that the latter possess the necessary genetic guidance that makes them intrinsically pluripotent. In contrast, vaPS cells do not have this intrinsic genetic guidance, but are able to differentiate into somatic cells of all three lineages under guidance of the microenvironment they are located in, independent from the original tissue or organ where they had resided. These vaPS cells are of high relevance for clinical application because they are contained in unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs). The latter can be obtained from and re-applied to the same patient at the point of care, without the need for further processing, manipulation, and culturing. These findings as well as various clinical examples presented in this paper demonstrate the potential of UA-ADRCs for enabling an entirely new generation of medicine for the benefit of patients and healthcare systems.
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Affiliation(s)
- Eckhard U. Alt
- Heart and Vascular Institute, Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA;
- Sanford School of Medicine, University of South Dakota, Sioux Falls, SD 57104, USA
- MD Anderson Cancer Center, University of Texas, Houston, TX 77054, USA
- Isar Klinikum Munich, 80331 Munich, Germany
| | - Christoph Schmitz
- Chair of Neuroanatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians University of Munich, 80336 Munich, Germany;
| | - Xiaowen Bai
- Heart and Vascular Institute, Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA;
- MD Anderson Cancer Center, University of Texas, Houston, TX 77054, USA
- Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA
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Alt E, Rothoerl R, Hoppert M, Frank HG, Wuerfel T, Alt C, Schmitz C. First immunohistochemical evidence of human tendon repair following stem cell injection: A case report and review of literature. World J Stem Cells 2021; 13:944-970. [PMID: 34367486 PMCID: PMC8316863 DOI: 10.4252/wjsc.v13.i7.944] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/29/2021] [Accepted: 06/25/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Current clinical treatment options for symptomatic, partial-thickness rotator cuff tear (sPTRCT) offer only limited potential for true tissue healing and improvement of clinical results. In animal models, injections of adult stem cells isolated from adipose tissue into tendon injuries evidenced histological regeneration of tendon tissue. However, it is unclear whether such beneficial effects could also be observed in a human tendon treated with fresh, uncultured, autologous, adipose derived regenerative cells (UA-ADRCs). A specific challenge in this regard is that UA-ADRCs cannot be labeled and, thus, not unequivocally identified in the host tissue. Therefore, histological regeneration of injured human tendons after injection of UA-ADRCs must be assessed using comprehensive, immunohistochemical and microscopic analysis of biopsies taken from the treated tendon a few weeks after injection of UA-ADRCs.
CASE SUMMARY A 66-year-old patient suffered from sPTRCT affecting the right supraspinatus and infraspinatus tendon, caused by a bicycle accident. On day 18 post injury [day 16 post magnetic resonance imaging (MRI) examination] approximately 100 g of abdominal adipose tissue was harvested by liposuction, from which approximately 75 × 106 UA-ADRCs were isolated within 2 h. Then, UA-ADRCs were injected (controlled by biplanar X-ray imaging) adjacent to the injured supraspinatus tendon immediately after isolation. Despite fast clinical recovery, a follow-up MRI examination 2.5 mo post treatment indicated the need for open revision of the injured infraspinatus tendon, which had not been treated with UA-ADRCs. During this operation, a biopsy was taken from the supraspinatus tendon at the position of the injury. A comprehensive, immunohistochemical and microscopic analysis of the biopsy (comprising 13 antibodies) was indicative of newly formed tendon tissue.
CONCLUSION Injection of UA-ADRCs can result in regeneration of injured human tendons by formation of new tendon tissue.
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Affiliation(s)
- Eckhard Alt
- Chairman of the Board, Isarklinikum Munich, Munich 80331, Germany
| | - Ralf Rothoerl
- Department of Spine Surgery, Isarklinikum Munich, Munich 80331, Germany
| | - Matthias Hoppert
- Department for Orthopedics and Trauma Surgery, Isarklinikum Munich, Munich 80331, Germany
| | - Hans-Georg Frank
- Chair of Neuroanatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Munich 80336, Germany
| | - Tobias Wuerfel
- Chair of Neuroanatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Munich 80336, Germany
| | - Christopher Alt
- Director of Science and Research, InGeneron GmbH, Munich 80331, Germany
| | - Christoph Schmitz
- Chair of Neuroanatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Munich 80336, Germany
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Rahimi-Sherbaf F, Nadri S, Rahmani A, Dabiri Oskoei A. Placenta mesenchymal stem cells differentiation toward neuronal-like cells on nanofibrous scaffold. ACTA ACUST UNITED AC 2020; 10:117-122. [PMID: 32363155 PMCID: PMC7186541 DOI: 10.34172/bi.2020.14] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 09/06/2019] [Accepted: 09/07/2019] [Indexed: 12/20/2022]
Abstract
Introduction: Transplantation of stem cells with a nanofibrous scaffold is a promising approach for spinal cord injury therapy. The aim of this work was to differentiate neural-like cells from placenta-derived mesenchymal stem cells (PDMSCs) using suitable induction reagents in three (3D) and two dimensional (2D) culture systems. Methods: After isolation and characterization of PDMSCs, the cells were cultivated on poly-L-lactide acid (PLLA)/poly caprolactone (PCL) nanofibrous scaffold and treated with a neuronal medium for 7 days. Electron microscopy, qPCR, and immunostaining were used to examine the differentiation of PDMSCs (on scaffold and tissue culture polystyrene [TCPS]) and the expression rate of neuronal markers (beta-tubulin, nestin, GFAP, and MAP-2). Results: qPCR analysis showed that beta-tubulin (1.672 fold; P ≤ 0.0001), nestin (11.145 fold; P ≤ 0.0001), and GFAP (80.171; P ≤ 0.0001) gene expressions were higher on scaffolds compared with TCPS. Immunofluorescence analysis showed that nestin and beta-tubulin proteins were recognized in the PDMSCs differentiated on TCPS and scaffold after 7 days in the neuroinductive differentiation medium. Conclusion: Taken together, these results delegated that PDMSCs differentiated on PLLA/PCL scaffolds are more likely to differentiate towards diversity lineages of neural cells. It proposed that PDMSCs have cell subpopulations that have the capability to be differentiated into neurogenic cells.
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Affiliation(s)
- Fatemeh Rahimi-Sherbaf
- Department of Obstetrics and Gynecology, School of Medicine, Yas Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Samad Nadri
- Department of Medical Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.,Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Ali Rahmani
- Department of Medical Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Atousa Dabiri Oskoei
- Department of Obstetrics and Gynecology, Mousavi Hospital, Zanjan University of Medical Sciences, Zanjan, Iran
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Mesenchymal Stem Cells in the Adult Human Liver: Hype or Hope? Cells 2019; 8:cells8101127. [PMID: 31546729 PMCID: PMC6830330 DOI: 10.3390/cells8101127] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 09/18/2019] [Accepted: 09/21/2019] [Indexed: 02/06/2023] Open
Abstract
Chronic liver diseases constitute a significant economic, social, and biomedical burden. Among commonly adopted approaches, only organ transplantation can radically help patients with end-stage liver pathologies. Cell therapy with hepatocytes as a treatment for chronic liver disease has demonstrated promising results. However, quality human hepatocytes are in short supply. Stem/progenitor cells capable of differentiating into functionally active hepatocytes provide an attractive alternative approach to cell therapy for liver diseases, as well as to liver-tissue engineering, drug screening, and basic research. The application of methods generally used to isolate mesenchymal stem cells (MSCs) and maintain them in culture to human liver tissue provides cells, designated here as liver MSCs. They have much in common with MSCs from other tissues, but differ in two aspects-expression of a range of hepatocyte-specific genes and, possibly, inherent commitment to hepatogenic differentiation. The aim of this review is to analyze data regarding liver MSCs, probably another type of liver stem/progenitor cells different from hepatic stellate cells or so-called hepatic progenitor cells. The review presents an analysis of the phenotypic characteristics of liver MSCs, their differentiation and therapeutic potential, methods for isolating these cells from human liver, and discusses issues of their origin and heterogeneity. Human liver MSCs are a fascinating object of fundamental research with a potential for important practical applications.
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Solakoglu Ö, Götz W, Kiessling MC, Alt C, Schmitz C, Alt EU. Improved guided bone regeneration by combined application of unmodified, fresh autologous adipose derived regenerative cells and plasma rich in growth factors: A first-in-human case report and literature review. World J Stem Cells 2019; 11:124-146. [PMID: 30842809 PMCID: PMC6397807 DOI: 10.4252/wjsc.v11.i2.124] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Revised: 12/07/2018] [Accepted: 01/10/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Novel strategies are needed for improving guided bone regeneration (GBR) in oral surgery prior to implant placement, particularly in maxillary sinus augmentation (GBR-MSA) and in lateral alveolar ridge augmentation (LRA). This study tested the hypothesis that the combination of freshly isolated, unmodified autologous adipose-derived regenerative cells (UA-ADRCs), fraction 2 of plasma rich in growth factors (PRGF-2) and an osteoinductive scaffold (OIS) (UA-ADRC/PRGF-2/OIS) is superior to the combination of PRGF-2 and the same OIS alone (PRGF-2/OIS) in GBR-MSA/LRA. CASE SUMMARY A 79-year-old patient was treated with a bilateral external sinus lift procedure as well as a bilateral lateral alveolar ridge augmentation. GBR-MSA/LRA was performed with UA-ADRC/PRGF-2/OIS on the right side, and with PRGF-2/OIS on the left side. Biopsies were collected at 6 wk and 34 wk after GBR-MSA/LRA. At the latter time point implants were placed. Radiographs (32 mo follow-up time) demonstrated excellent bone healing. No radiological or histological signs of inflammation were observed. Detailed histologic, histomorphometric, and immunohistochemical analysis of the biopsies evidenced that UA-ADRC/PRGF-2/OIS resulted in better and faster bone regeneration than PRGF-2/OIS. CONCLUSION GBR-MSA with UA-ADRCs, PRGF-2, and an OIS shows effectiveness without adverse effects.
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Affiliation(s)
- Önder Solakoglu
- External Visiting Lecturer, Dental Department of the University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
- Clinic for Periodontology and Implantology, Hamburg 22453, Germany.
| | - Werner Götz
- Department of Orthodontics, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn 53111, Germany
| | - Maren C Kiessling
- Institute of Anatomy, Faculty of Medicine, LMU Munich, Munich 80336, Germany
| | | | - Christoph Schmitz
- Institute of Anatomy, Faculty of Medicine, LMU Munich, Munich 80336, Germany
| | - Eckhard U Alt
- InGeneron GmbH, Munich 80331, Germany
- InGeneron, Inc., Houston, TX 77054, United States
- Isar Klinikum Munich, 80331 Munich, Germany
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Effects of palmitate and astaxanthin on cell viability and proinflammatory characteristics of mesenchymal stem cells. Int Immunopharmacol 2019; 68:164-170. [PMID: 30639962 DOI: 10.1016/j.intimp.2018.12.063] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Revised: 12/16/2018] [Accepted: 12/28/2018] [Indexed: 12/18/2022]
Abstract
Mesenchymal stem cells (MSCs) have broad immunomodulatory activities. These cells are a stable source of cytokine production such as interleukin-6 (IL6), monocyte chemoattractant protein-1 (MCP-1/CCL2) and vascular endothelial growth factor (VEGF). Fatty acid elevation in chronic metabolic diseases alters the microenvironment of MSCs and thereby, might affect their survival and cytokine production. In the present study, we investigated the effects of palmitate, the most abundant saturated free fatty acid (FFA) in plasma, and astaxanthin, a potent antioxidant, on cell viability and apoptosis in human bone marrow-driven mesenchymal stem cells. We also elucidated how palmitate and astaxanthin influence the inflammation in MSCs. Human mesenchymal stem cells were collected from an aspirate of the femurs and tibias marrow compartment. The effect of palmitate on cell viability, caspase activity and pro-inflammatory cytokines expression and secretion were evaluated. In addition, activation of the MAP kinases and NF-kB signaling pathways were investigated. The results showed that astaxanthin protected MSCs from palmitate-induced cell death. We found that palmitate significantly enhanced IL-6, VEGF and MCP-1 expression, and secretion in MSC cells. Increased cytokine expression was parallel to the enhanced phosphorylation of P38, ERK and IKKα-IKKβ. In addition, pretreatment with JNK, ERK, P38, and NF-kB inhibitors could correspondingly attenuate palmitate-induced expression of VEGF, IL-6, and MCP-1. Our results demonstrated that fatty acid exposure causes inflammatory responses in MSCs that can be alleviated favorably by astaxanthin treatment.
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di Bello G, Vendemiale G, Bellanti F. Redox cell signaling and hepatic progenitor cells. Eur J Cell Biol 2018; 97:546-556. [PMID: 30278988 DOI: 10.1016/j.ejcb.2018.09.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 09/20/2018] [Accepted: 09/20/2018] [Indexed: 02/08/2023] Open
Abstract
Hepatic diseases are widespread in the world and organ transplantation is currently the only treatment for liver failure. New cell-based approaches have been considered, since stem cells may represent a possible source to treat liver diseases. Acute and chronic liver diseases are characterized by high production of reactive oxygen and nitrogen species, with consequent oxidative modifications of cellular macromolecules and alteration of signaling pathways, metabolism and cell cycle. Although considered harmful molecules, reactive species are involved in cell growth and differentiation processes, modulating the activity of transcription factors, which take part in stemness/proliferation. It is conceivable that redox balance may regulate the development of hepatic progenitor cells, function and survival in synchrony with metabolism during chronic liver diseases. This review aims to summarize diverse redox-sensitive signaling pathways involved in stem cell fate, highlighting the important role of hepatic progenitor cells as a possible source to treat end-stage liver disease for organ regeneration.
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Affiliation(s)
- Giorgia di Bello
- Centre for Experimental and Regenerative Medicine, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Italy
| | - Gianluigi Vendemiale
- Centre for Experimental and Regenerative Medicine, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Italy
| | - Francesco Bellanti
- Centre for Experimental and Regenerative Medicine, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Italy.
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Comparison of Hematopoietic and Spermatogonial Stem Cell Niches from the Regenerative Medicine Aspect. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1107:15-40. [PMID: 29882209 DOI: 10.1007/5584_2018_217] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Strategies to Enhance the Effectiveness of Adult Stem Cell Therapy for Ischemic Heart Diseases Affecting the Elderly Patients. Stem Cell Rev Rep 2017; 12:214-23. [PMID: 26779896 DOI: 10.1007/s12015-016-9642-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Myocardial infarctions and chronic ischemic heart disease both commonly and disproportionately affect elderly patients more than any other patient population. Despite available treatments, heart tissue is often permanently damaged as a result of cardiac injury. This review aims to summarize recent literature proposing the use of modified autologous adult stem cells to promote healing of post-infarct cardiac tissue. This novel cellular treatment involves isolation of adult stem cells from the patient, in vitro manipulation of these stem cells, and subsequent transplantation back into the patient's own heart to accelerate healing. One of the hindrances affecting this process is that cardiac issues are increasingly common in elderly patients, and stem cells recovered from their tissues tend to be pre-senescent or already in senescence. As a result, harsh in vitro manipulations can cause the aged stem cells to undergo massive in vivo apoptosis after transplantation. The consensus in literature is that inhibition or reversal of senescence onset in adult stem cells would be of utmost benefit. In fact, it is believed that this strategy may lower stem cell mortality and coerce aged stem cells into adopting more resilient phenotypes similar to that of their younger counterparts. This review will discuss a selection of the most efficient and most-recent strategies used experimentally to enhance the effectiveness of current stem cell therapies for ischemic heart diseases.
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Han S, Xiao Z, Li X, Zhao H, Wang B, Qiu Z, Li Z, Mei X, Xu B, Fan C, Chen B, Han J, Gu Y, Yang H, Shi Q, Dai J. Human placenta-derived mesenchymal stem cells loaded on linear ordered collagen scaffold improves functional recovery after completely transected spinal cord injury in canine. SCIENCE CHINA-LIFE SCIENCES 2017; 61:2-13. [PMID: 28527111 DOI: 10.1007/s11427-016-9002-6] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Accepted: 05/12/2017] [Indexed: 02/07/2023]
Abstract
Traumatic spinal cord injury (SCI) is a major challenge in the clinic. In this study, we sought to examine the synergistic effects of linear ordered collagen scaffold (LOCS) and human placenta-derived mesenchymal stem cells (hPMSCs) when transplanted into completely transected beagle dogs. After 36 weeks observation, we found that LOCS+hPMSCs implants promoted better hindlimb locomotor recovery than was observed in the non-treatment (control) group and LOCS group. Histological analysis showed that the regenerated tissue after treatment was well integrated with the host tissue, and dramatically reduced the volume of cystic and chondroitin sulfate proteoglycans (CSPGs) expression. Furthermore, the LOCS+hPMSCs group also showed more neuron-specific βIII-tubulin (Tuj-1)- and NeuN-positive neurons in the lesion area, as well as axonal regeneration, remyelination and synapse formation in the lesion site. Additionally, dogs in the LOCS+hPMSCs group experienced enhanced sprouting of both ascending (CGRP-positive) sensory fibers and descending (5-HT- and TH-positive) motor fibers at the lesion area. All these data together suggested that the combined treatment had beneficial effects on neuronal regeneration and functional improvement in a canine complete transection model. Therefore, LOCS+hPMSCs implantation holds a great promise for bridging the nerve defect and may be clinically useful in the near future.
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Affiliation(s)
- Sufang Han
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China
| | - Zhifeng Xiao
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China
| | - Xing Li
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China
| | - Huan Zhao
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Orthopaedic Institute, Soochow University, Suzhou, 215006, China
| | - Bin Wang
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China
| | - Zhixue Qiu
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Orthopaedic Institute, Soochow University, Suzhou, 215006, China
| | - Zhi Li
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Orthopaedic Institute, Soochow University, Suzhou, 215006, China
| | - Xin Mei
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Orthopaedic Institute, Soochow University, Suzhou, 215006, China
| | - Bai Xu
- Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China
| | - Caixia Fan
- Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China
| | - Bing Chen
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China
| | - Jin Han
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China
| | - Yanzheng Gu
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Orthopaedic Institute, Soochow University, Suzhou, 215006, China
| | - Huilin Yang
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Orthopaedic Institute, Soochow University, Suzhou, 215006, China
| | - Qin Shi
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Orthopaedic Institute, Soochow University, Suzhou, 215006, China.
| | - Jianwu Dai
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China.
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Ti D, Hao H, Fu X, Han W. Mesenchymal stem cells-derived exosomal microRNAs contribute to wound inflammation. SCIENCE CHINA-LIFE SCIENCES 2016; 59:1305-1312. [PMID: 27864711 DOI: 10.1007/s11427-016-0240-4] [Citation(s) in RCA: 106] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Accepted: 10/16/2016] [Indexed: 12/23/2022]
Abstract
Clinical and experimental studies have highlighted the significance of inflammation in coordinating wound repair and regeneration. However, it remains challenging to control the inflammatory response and tolerance at systemic levels without causing toxicity to injured tissues. Mesenchymal stem cells (MSCs) possess potent immunomodulatory properties and facilitate tissue repair by releasing exosomes, which generate a suitable microenvironment for inflammatory resolution. Exosomes contain several effective bioactive molecules and act as a cell-cell communication vehicle to influence cellular activities in recipient cells. During this process, the horizontal transfer of exosomal microRNAs (miRNAs) to acceptor cells, where they regulate target gene expression, is of particular interest for understanding the basic biology of inflammation ablation, tissue homeostasis, and development of therapeutic approaches. In this review, we describe a signature of three specific miRNAs (miR-21, miR-146a, and miR-181) present in human umbilical cord MSC-derived exosomes (MSC-EXO) identified microarray chip analysis and focus on the inflammatory regulatory functions of these immune-related miRNAs. We also discuss the potential mechanisms contributing to the resolution of wound inflammation and tissue healing.
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Affiliation(s)
- Dongdong Ti
- Institute of Basic Medicine, College of Life Sciences, Chinese PLA General Hospital, Beijing, 100853, China
| | - Haojie Hao
- Institute of Basic Medicine, College of Life Sciences, Chinese PLA General Hospital, Beijing, 100853, China
| | - Xiaobing Fu
- Institute of Basic Medicine, College of Life Sciences, Chinese PLA General Hospital, Beijing, 100853, China.
| | - Weidong Han
- Institute of Basic Medicine, College of Life Sciences, Chinese PLA General Hospital, Beijing, 100853, China.
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