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Lakshminarayanan A, Kannan S, Kuppusamy MK, Sankaranarayanan K, Godla U, Punnoose AM. The effect of curcumin, catechin and resveratrol on viability, proliferation and cytotoxicity of human umbilical cord Wharton's jelly derived mesenchymal stem cells. Tissue Cell 2025; 93:102742. [PMID: 39874919 DOI: 10.1016/j.tice.2025.102742] [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: 09/13/2024] [Revised: 01/11/2025] [Accepted: 01/11/2025] [Indexed: 01/30/2025]
Abstract
INTRODUCTION Mesenchymal stem cells possess the capability to proliferate and differentiate into diverse lineages. Their beneficial properties have been explored widely to treat various disorders. Phytochemicals like curcumin, catechin and resveratrol have been evaluated for their medicinal values and have promising potential in treating numerous diseases. In this study, we have elucidated the in vitro survival, proliferative and cytotoxic effects of these phytochemicals at selected range of concentrations on human umbilical cord derived Wharton's jelly mesenchymal stem cells (WJ-MSCs). METHODS The human WJ-MSCs were extracted using explant culture method and characterized as per International Society for Cellular Therapy (ISCT) guidelines. To analyse the effect of different phytochemicals, the WJ-MSCs were treated with various concentrations ranging from 0.1 to 1000 µM and the viability, proliferative and toxicity effects were assayed using (3-(4,5-dimethylthioazolyl-2,5-diphenyltetrozolium bromide) MTT. RESULTS Curcumin and catechin elicited no cytotoxic effect on WJ-MSCs after 48 hours of treatment between the concentrations ranging from 0.1 to 10 µM and the viability was maintained above 80 %. For both the phytochemicals, there was a significant decrease in the viability of WJ-MSCs after 50 µM. Resveratrol was well tolerated at higher doses till 100 µM with a viability above 90 % and cytotoxic effect was observed above 250 µM. CONCLUSION Curcumin, catechin and resveratrol, affect the viability and proliferation of WJ-MSCs differently at varying concentrations. This data will be useful in deciding the dose of phytochemicals when employed concomitantly with stem cells to increase their efficiency.
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Affiliation(s)
- Aishwarya Lakshminarayanan
- Stem Cell and Regenerative Biology Laboratory, Faculty of Clinical Research, Sri Ramachandra Institute of Higher Education and Research, India
| | | | - M Kalaivani Kuppusamy
- Faculty of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research, India
| | | | - Usharani Godla
- Obstetrics and Gynecology, Sri Ramachandra Medical Centre, India
| | - Alan M Punnoose
- Stem Cell and Regenerative Biology Laboratory, Faculty of Clinical Research, Sri Ramachandra Institute of Higher Education and Research, India.
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2
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Zou X, Brigstock D. Extracellular Vesicles from Mesenchymal Stem Cells: Potential as Therapeutics in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Biomedicines 2024; 12:2848. [PMID: 39767754 PMCID: PMC11673942 DOI: 10.3390/biomedicines12122848] [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: 11/11/2024] [Revised: 12/06/2024] [Accepted: 12/12/2024] [Indexed: 01/03/2025] Open
Abstract
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by the accumulation of triglycerides within hepatocytes, which can progress to more severe conditions, such as metabolic dysfunction-associated steatohepatitis (MASH), which may include progressive fibrosis, leading to cirrhosis, cancer, and death. This goal of this review is to highlight recent research showing the potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in reducing the key pathogenic pathways of MASLD or MASH. Methods: Relevant published studies were identified using PubMed with one or more of the following search terms: MASLD, MASH, NAFLD, NASH, exosome, extracellular vesicle (EV), therapy, and/or mesenchymal stem cells (MSC). The primary literature were subsequently downloaded and summarized. Results: Using in vitro or in vivo models, MSC-EVs have been found to counteract oxidative stress, a significant contributor to liver injury in MASH, and to suppress disease progression, including steatosis, inflammation, and, in a few instances, fibrosis. Some of these outcomes have been attributed to specific EV cargo components including microRNAs and proteins. Thus, MSC-EVs enriched with these types of molecules may have improved the therapeutic efficacy for MASLD/MASH and represent a novel approach to potentially halt or reverse the disease process. Conclusions: MSC-EVs are attractive therapeutic agents for treating MASLD/MASH. Further studies are necessary to validate the clinical applicability and efficacy of MSC-EVs in human MASH patients, focusing on optimizing delivery strategies and identifying the pathogenic pathways that are targeted by specific EV components.
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Affiliation(s)
- Xue Zou
- Center for Clinical and Translational Research, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USA;
| | - David Brigstock
- Center for Clinical and Translational Research, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USA;
- Department of Surgery, Wexner Medical Center, The Ohio State University, Columbus, OH 43212, USA
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Ge Z, Qiu C, Zhou J, Yang Z, Jiang T, Yuan W, Yu L, Li J. Proteomic analysis of human Wharton's jelly mesenchymal stem/stromal cells and human amniotic epithelial stem cells: a comparison of therapeutic potential. Sci Rep 2024; 14:28061. [PMID: 39543366 PMCID: PMC11564572 DOI: 10.1038/s41598-024-79063-1] [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: 08/15/2024] [Accepted: 11/06/2024] [Indexed: 11/17/2024] Open
Abstract
Perinatal stem cells have prominent applications in cell therapy and regenerative medicine. Among them, human Wharton's jelly mesenchymal stem/stromal cells (hWJMSCs) and human amniotic epithelial stem cells (hAESCs) have been widely used. However, the distinction in the therapeutic potential of hWJMSCs and hAESCs is poorly understood. In this study, we reported the phenotypic differences between these two distinct cell types and provided the first systematic comparison of their therapeutic potential in terms of immunomodulation, extracellular matrix (ECM) remodelling, angiogenesis and antioxidative stress using proteomics. The results revealed that the two cell types presented different protein expression profiles and were both promising candidates for cell therapy. Both types of cells demonstrated angiogenic and antifibrotic potential, whereas hAESCs presented superior immunological tolerance and antioxidant properties, which were supported by a series of relevant in vitro assays. Our study provides clues for the selection of appropriate cell types for diverse indications in cell therapy, which contributes to the advancement of their clinical translation and application.
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Affiliation(s)
- Zhen Ge
- Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, 310013, Zhejiang, China
| | - Chen Qiu
- Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine of Sir Run Run Shaw Hospital, Zhejiang University-Lishui Joint Innovation Center for Life and Health, Zhejiang University, Hangzhou, 310058, China
- College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Joint Research Centre for Engineering Biology, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, 314400, China
| | - Jiayi Zhou
- Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine of Sir Run Run Shaw Hospital, Zhejiang University-Lishui Joint Innovation Center for Life and Health, Zhejiang University, Hangzhou, 310058, China
- College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Joint Research Centre for Engineering Biology, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, 314400, China
| | - Zhuoheng Yang
- Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine of Sir Run Run Shaw Hospital, Zhejiang University-Lishui Joint Innovation Center for Life and Health, Zhejiang University, Hangzhou, 310058, China
- College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Joint Research Centre for Engineering Biology, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, 314400, China
| | - Tuoying Jiang
- Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine of Sir Run Run Shaw Hospital, Zhejiang University-Lishui Joint Innovation Center for Life and Health, Zhejiang University, Hangzhou, 310058, China
- College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Joint Research Centre for Engineering Biology, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, 314400, China
| | - Weixin Yuan
- College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Joint Research Centre for Engineering Biology, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, 314400, China
| | - Luyang Yu
- Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine of Sir Run Run Shaw Hospital, Zhejiang University-Lishui Joint Innovation Center for Life and Health, Zhejiang University, Hangzhou, 310058, China.
- College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Joint Research Centre for Engineering Biology, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, 314400, China.
| | - Jinying Li
- Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine of Sir Run Run Shaw Hospital, Zhejiang University-Lishui Joint Innovation Center for Life and Health, Zhejiang University, Hangzhou, 310058, China.
- College of Life Sciences-iCell Biotechnology Regenerative Biomedicine Laboratory, Joint Research Centre for Engineering Biology, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, 314400, China.
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Bhatta MP, Won GW, Lee SH, Choi SH, Oh CH, Moon JH, Hoang HH, Lee J, Lee SD, Park JI. Determination of adipogenesis stages of human umbilical cord-derived mesenchymal stem cells using three-dimensional label-free holotomography. Methods 2024; 231:204-214. [PMID: 39395684 DOI: 10.1016/j.ymeth.2024.10.005] [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: 09/06/2024] [Revised: 10/07/2024] [Accepted: 10/09/2024] [Indexed: 10/14/2024] Open
Abstract
Adipogenesis involves complex changes in gene expression, morphology, and cytoskeletal organization. However, the quantitative analysis of live cell images to identify their stages through morphological markers is limited. Distinct adipogenesis markers on human umbilical cord-derived mesenchymal stem cells (UC-MSCs) were identified through holotomography, a label-free live cell imaging technique. In the MSC-to-preadipocyte transition, the nucleus-to-cytoplasm ratio (0.080 vs. 0.052) and lipid droplet (LD) refractive index variation decreased (0.149 % vs. 0.061 %), whereas the LD number (20 vs. 65) increased. This event was also accompanied by the downregulation and upregulation of THY1 and Preadipocyte Factor-1 (PREF-1), respectively. In the preadipocyte to immature adipocyte shift, cell sphericity (0.20 vs. 0.43) and LD number (65 vs. 200) surged, large LDs (>10 μm3) appeared, and the major axis of the cell was reduced (143.7 μm vs. 83.12 μm). These findings indicate features of preadipocyte and immature adipocyte stages, alongside the downregulation of PREF-1 and upregulation of Peroxisome Proliferator-Activated Receptor gamma (PPARγ). In adipocyte maturation, along with PPARγ and Fatty Acid-Binding Protein 4 upregulation, cell compactness (0.15 vs. 0.29) and sphericity (0.43 vs. 0.59) increased, and larger LDs (>30 μm3) formed, marking immature and mature adipocyte stages. The study highlights the distinct adipogenic morphological biomarkers of adipogenesis stages in UC-MSCs, providing potential applications in biomedical and clinical settings, such as fostering innovative medical strategies for treating metabolic disease.
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Affiliation(s)
- Mahesh Prakash Bhatta
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea; Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea; Brain Korea 21 FOUR Project for Medical Science, Chungnam National University, Daejeon 35015, Republic of Korea
| | - Gun-Woo Won
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea
| | - Seung Hoon Lee
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea; Translational Immunology Institute, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea
| | - Seung-Hyeon Choi
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea; Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea; Brain Korea 21 FOUR Project for Medical Science, Chungnam National University, Daejeon 35015, Republic of Korea
| | - Cheong-Hae Oh
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea
| | - Ji Hyun Moon
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea
| | | | | | - Sang Do Lee
- Department of Physiology, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.
| | - Jong-Il Park
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea; Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea; Brain Korea 21 FOUR Project for Medical Science, Chungnam National University, Daejeon 35015, Republic of Korea; Translational Immunology Institute, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea.
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Sheikhbahaei F, Shams P, Seyyedin S, Shojaei M, Nematollahi-Mahani SN. The order of green and red LEDs irradiation affects the neural differentiation of human umbilical cord matrix-derived mesenchymal cells. Sci Rep 2024; 14:21107. [PMID: 39256554 PMCID: PMC11387487 DOI: 10.1038/s41598-024-72099-3] [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: 03/21/2024] [Accepted: 09/03/2024] [Indexed: 09/12/2024] Open
Abstract
Different wavelengths emitted from light-emitting diodes (LEDs) are known as an influential factor in proliferation and differentiation of various cell types. Since human umbilical cord matrix-derived mesenchymal cells (hUCMs) are ideal tools for human regenerative medicine clinical trials and stem cell researches, in the present study we investigated the neurogenesis effects of single and intermittent green and red LED irradiation on hUCM cells. Exposure of hUCMs to single and intermittent green (530 nm, 1.59 J/cm2) and red (630 nm, 0.318 J/cm2) lights significantly increased the expression of specific genes including nestin, β-tubulin III and Olig2. Additionally, immunocytochemical analysis confirmed the expression of specific neural-related proteins including nestin, β-tubulin III, Olig2 and GFAP. Also, alternating exposure of hUCM cells to green and red lights increased the expression of some neural markers more than either light alone. Further research are required to develop the application of LED irradiation as a useful tool for therapeutic purposes including neural repair and regeneration.
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Affiliation(s)
- Fatemeh Sheikhbahaei
- Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Parisa Shams
- Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Sajad Seyyedin
- Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Seyed Noureddin Nematollahi-Mahani
- Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
- Kerman Neuroscience Research Center (KNRC), Institute of Neuropharmacology, Kerman University of Medical Sciences, Somayeh Cross, Avicenna St., Kerman, 76198-13159, Iran.
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6
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Younesi FS, Hinz B. The Myofibroblast Fate of Therapeutic Mesenchymal Stromal Cells: Regeneration, Repair, or Despair? Int J Mol Sci 2024; 25:8712. [PMID: 39201399 PMCID: PMC11354465 DOI: 10.3390/ijms25168712] [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: 06/21/2024] [Revised: 07/31/2024] [Accepted: 08/06/2024] [Indexed: 09/02/2024] Open
Abstract
Mesenchymal stromal cells (MSCs) can be isolated from various tissues of healthy or patient donors to be retransplanted in cell therapies. Because the number of MSCs obtained from biopsies is typically too low for direct clinical application, MSC expansion in cell culture is required. However, ex vivo amplification often reduces the desired MSC regenerative potential and enhances undesired traits, such as activation into fibrogenic myofibroblasts. Transiently activated myofibroblasts restore tissue integrity after organ injury by producing and contracting extracellular matrix into scar tissue. In contrast, persistent myofibroblasts cause excessive scarring-called fibrosis-that destroys organ function. In this review, we focus on the relevance and molecular mechanisms of myofibroblast activation upon contact with stiff cell culture plastic or recipient scar tissue, such as hypertrophic scars of large skin burns. We discuss cell mechanoperception mechanisms such as integrins and stretch-activated channels, mechanotransduction through the contractile actin cytoskeleton, and conversion of mechanical signals into transcriptional programs via mechanosensitive co-transcription factors, such as YAP, TAZ, and MRTF. We further elaborate how prolonged mechanical stress can create persistent myofibroblast memory by direct mechanotransduction to the nucleus that can evoke lasting epigenetic modifications at the DNA level, such as histone methylation and acetylation. We conclude by projecting how cell culture mechanics can be modulated to generate MSCs, which epigenetically protected against myofibroblast activation and transport desired regeneration potential to the recipient tissue environment in clinical therapies.
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Affiliation(s)
- Fereshteh Sadat Younesi
- Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canada;
- Keenan Research Institute for Biomedical Science, St. Michael’s Hospital, Toronto, ON M5B 1T8, Canada
| | - Boris Hinz
- Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canada;
- Keenan Research Institute for Biomedical Science, St. Michael’s Hospital, Toronto, ON M5B 1T8, Canada
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7
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Sharma P, Maurya DK. Wharton's jelly mesenchymal stem cells: Future regenerative medicine for clinical applications in mitigation of radiation injury. World J Stem Cells 2024; 16:742-759. [PMID: 39086560 PMCID: PMC11287430 DOI: 10.4252/wjsc.v16.i7.742] [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: 03/18/2024] [Revised: 05/28/2024] [Accepted: 06/24/2024] [Indexed: 07/25/2024] Open
Abstract
Wharton's jelly mesenchymal stem cells (WJ-MSCs) are gaining significant attention in regenerative medicine for their potential to treat degenerative diseases and mitigate radiation injuries. WJ-MSCs are more naïve and have a better safety profile, making them suitable for both autologous and allogeneic transplantations. This review highlights the regenerative potential of WJ-MSCs and their clinical applications in mitigating various types of radiation injuries. In this review, we will also describe why WJ-MSCs will become one of the most probable stem cells for future regenerative medicine along with a balanced view on their strengths and weaknesses. Finally, the most updated literature related to both preclinical and clinical usage of WJ-MSCs for their potential application in the regeneration of tissues and organs will also be compiled.
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Affiliation(s)
- Prashasti Sharma
- Life Sciences, Homi Bhabha National Institute, Mumbai 400094, Maharashtra, India
- Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085, Maharashtra, India
| | - Dharmendra Kumar Maurya
- Life Sciences, Homi Bhabha National Institute, Mumbai 400094, Maharashtra, India
- Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085, Maharashtra, India.
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8
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Goushki MA, Kharat Z, Kehtari M, Sohi AN, Ahvaz HH, Rad I, HosseinZadeh S, Kouhkan F, Kabiri M. Applications of extraembryonic tissue-derived cells in vascular tissue regeneration. Stem Cell Res Ther 2024; 15:205. [PMID: 38982541 PMCID: PMC11234723 DOI: 10.1186/s13287-024-03784-3] [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: 02/29/2024] [Accepted: 06/06/2024] [Indexed: 07/11/2024] Open
Abstract
Vascular tissue engineering is a promising approach for regenerating damaged blood vessels and developing new therapeutic approaches for heart disease treatment. To date, different sources of cells have been recognized that offer assistance within the recovery of heart supply routes and veins with distinctive capacities and are compelling for heart regeneration. However, some challenges still remain that need to be overcome to establish the full potential application of these cells. In this paper, we review the different cell sources used for vascular tissue engineering, focusing on extraembryonic tissue-derived cells (ESCs), and elucidate their roles in cardiovascular disease. In addition, we highlight the intricate interplay between mechanical and biochemical factors in regulating mesenchymal stem cell (MSC) differentiation, offering insights into optimizing their application in vascular tissues.
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Affiliation(s)
- Mehdi Amiri Goushki
- Department of Life Science Engineering, Faculty of New Sciences & Technologies, University of Tehran, Tehran, 14395-1561, Iran
| | - Zahra Kharat
- Department of Life Science Engineering, Faculty of New Sciences & Technologies, University of Tehran, Tehran, 14395-1561, Iran
| | - Mousa Kehtari
- School of Biology, College of Sciences, University of Tehran, Tehran, 1417614411, Iran
| | - Alireza Naderi Sohi
- National Institute of Genetic Engineering and Biotechnology, Tehran, 1497716316, Iran
| | | | - Iman Rad
- Stem Cell Technology Research Center, Tehran, 15856-36473, Iran
| | - Simzar HosseinZadeh
- Department of Tissue Engineering and Regenerative Medicine, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Kouhkan
- Stem Cell Technology Research Center, Tehran, 15856-36473, Iran
| | - Mahboubeh Kabiri
- Department of Biotechnology, College of Science, University of Tehran, Tehran, 14155-6455, Iran.
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Wu SH, Yu JH, Liao YT, Chou PH, Wen MH, Hsueh KK, Wang JP. Comparison of infant bone marrow- and umbilical cord-derived mesenchymal stem cells in multilineage differentiation. Regen Ther 2024; 26:837-849. [PMID: 39430580 PMCID: PMC11488484 DOI: 10.1016/j.reth.2024.09.011] [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: 07/30/2024] [Revised: 09/15/2024] [Accepted: 09/25/2024] [Indexed: 10/22/2024] Open
Abstract
We compared infant bone marrow-derived mesenchymal stem cells (infant BMSCs) with umbilical cord-derived mesenchymal stem cells (UCSCs) by assessing multilineage differentiation. Proliferation was gauged through changes in cell numbers and doubling time. Senescence-related genes (p16, p21, and p53), senescence-associated β-galactosidase (SA-β-gal), and γH2AX immunofluorescence determined senescence presence. Superoxide dismutases (SODs) and genes related to various differentiations were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Differentiation was confirmed through histochemical, immunohistochemical, and immunofluorescence staining. Infant BMSCs surpassed UCSCs in proliferation. Infant BMSCs exhibited lower senescence-related gene expression at late passages, upregulated antioxidant enzymes during early passages, and reduced SA-β-gal staining. Chondrogenic gene expression (SOX9, COL2, and COL10) was enhanced in infant BMSCs, along with improved immunohistochemical staining. Infant BMSCs showed higher expression of osteogenic (ALP and OCN) and adipogenic (PPARγ and LPL) genes, confirmed by histochemical staining. However, UCSCs had higher expression of tenogenic genes (MMP3, SCX, DCN, and TNC). Hepatogenic differentiation potential was similar, with no significant difference in hepatogenic gene expression (ALB and TAT). Compared to UCSCs, infant BMSCs demonstrated superior proliferation, reduced senescence, increased antioxidant capacity, and enhanced differentiation potential toward chondrogenic, osteogenic, and adipogenic lineages.
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Affiliation(s)
- Szu-Hsien Wu
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, National Defense Medical Center, Taipei, Taiwan
| | - Jin-Huei Yu
- Department of Orthopedic Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
| | - Yu-Ting Liao
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Orthopaedics & Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Po-Hsin Chou
- Department of Orthopaedics & Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ming-Hsuan Wen
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Orthopaedics & Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Kuang-Kai Hsueh
- Department of Orthopedic Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
| | - Jung-Pan Wang
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Orthopaedics & Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan
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Maličev E, Jazbec K. An Overview of Mesenchymal Stem Cell Heterogeneity and Concentration. Pharmaceuticals (Basel) 2024; 17:350. [PMID: 38543135 PMCID: PMC10975472 DOI: 10.3390/ph17030350] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 02/22/2024] [Accepted: 03/05/2024] [Indexed: 01/06/2025] Open
Abstract
Mesenchymal stem cells (MSCs) are of great interest in cell therapies due to the immunomodulatory and other effects they have after autologous or allogeneic transplantation. In most clinical applications, a high number of MSCs is required; therefore, the isolated MSC population must be expanded in the cell culture until the desired number is reached. Analysing freshly isolated MSCs is challenging due to their rareness and heterogeneity, which is noticeable among donors, tissues, and cell subpopulations. Although the phenotype of MSCs in tissue can differ from those of cultured cells, phenotyping and counting are usually performed only after MSC proliferation. As MSC applicability is a developing and growing field, there is a need to implement phenotyping and counting methods for freshly isolated MSCs, especially in new one-step procedures where isolated cells are implanted immediately without cell culturing. Only by analysing harvested cells can we correctly evaluate such studies. This review describes multilevel heterogeneity and concentrations of MSCs and different strategies for phenotype determination and enumeration of freshly isolated MSCs.
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Affiliation(s)
- Elvira Maličev
- Blood Transfusion Centre of Slovenia, Šlajmerjeva 6, 1000 Ljubljana, Slovenia;
- Biotechnical Faculty, University of Ljubljana, Jamnikarjeva ulica 101, 1000 Ljubljana, Slovenia
| | - Katerina Jazbec
- Blood Transfusion Centre of Slovenia, Šlajmerjeva 6, 1000 Ljubljana, Slovenia;
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Shen J, Wu L, Shi X, Chen G, Liu T, Xu F, Xu X, Kou X, Zhao Y, Wang H, Wang C, Gao S, Xu S. Transplantation of the LRP1 high subpopulation of human umbilical cord-derived mesenchymal stem cells improves ovarian function in mice with premature ovarian failure and aged mice. Stem Cell Res Ther 2024; 15:64. [PMID: 38438896 PMCID: PMC10913679 DOI: 10.1186/s13287-024-03660-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 02/07/2024] [Indexed: 03/06/2024] Open
Abstract
BACKGROUND Premature ovarian failure (POF) has a profound impact on female reproductive and psychological health. In recent years, the transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) has demonstrated unprecedented potential in the treatment of POF. However, the heterogeneity of human UC-MSCs remains a challenge for their large-scale clinical application. Therefore, it is imperative to identify specific subpopulations within UC-MSCs that possess the capability to improve ovarian function, with the aim of reducing the uncertainty arising from the heterogeneity while achieving more effective treatment of POF. METHODS 10 × Genomics was performed to investigate the heterogeneity of human UC-MSCs. We used LRP1 as a marker and distinguished the potential therapeutic subpopulation by flow cytometry, and determined its secretory functions. Unsorted UC-MSCs, LRP1high and LRP1low subpopulation was transplanted under the ovarian capsules of aged mice and CTX-induced POF mice, and therapeutic effects was evaluated by assessing hormone levels, estrous cycles, follicle counts, and embryo numbers. RNA sequencing on mouse oocytes and granulosa cells after transplantation was performed to explore the mechanism of LRP1high subpopulation on mouse oocytes and granulosa cells. RESULTS We identified three distinct functional subtypes, including mesenchymal stem cells, multilymphoid progenitor cells and trophoblasts. Additionally, we identified the LRP1high subpopulation, which improved ovarian function in aged and POF mice. We elucidated the unique secretory functions of the LRP1high subpopulation, capable of secreting various chemokines, cytokines, and growth factors. Furthermore, LRP1 plays a crucial role in regulating the ovarian microenvironment, including tissue repair and extracellular matrix remodeling. Consistent with its functions, the transcriptomes of oocytes and granulosa cells after transplantation revealed that the LRP1high subpopulation improves ovarian function by modulating the extracellular matrix of oocytes, NAD metabolism, and mitochondrial function in granulosa cells. CONCLUSION Through exploration of the heterogeneity of UC-MSCs, we identified the LRP1high subpopulation capable of improving ovarian function in aged and POF mice by secreting various factors and remodeling the extracellular matrix. This study provides new insights into the targeted exploration of human UC-MSCs in the precise treatment of POF.
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Affiliation(s)
- Jiacheng Shen
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China
| | - Li Wu
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
| | - Xiaoying Shi
- Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital, School of Life Science and Technology, Tongji University, Tongji, 200092, China
- Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China
| | - Gang Chen
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China
| | - Tingwei Liu
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China
| | - Fangfang Xu
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China
| | - Xiaocui Xu
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China
| | - Xiaochen Kou
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China
- Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China
| | - Yanhong Zhao
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China
- Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China
| | - Hong Wang
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China
- Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China
| | - Chenfei Wang
- Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital, School of Life Science and Technology, Tongji University, Tongji, 200092, China
- Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China
| | - Shaorong Gao
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
- Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
| | - Shaohua Xu
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
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Ha GH, Yeon JY, Kim KH, Lee DM, Chae HY, Nam H, Lee K, Kim DO, Kim CK, Joo KM. Thrombin Priming Promotes the Neuroprotective Effects of Human Wharton's Jelly-Derived Mesenchymal Stem Cells Via the HGF/AKT/STAT3 Signaling Pathway. Stem Cells Dev 2024; 33:89-103. [PMID: 38164089 DOI: 10.1089/scd.2023.0191] [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: 01/03/2024] Open
Abstract
Mesenchymal stem cells (MSCs) directly differentiate into neurons and endothelial cells after transplantation, and their secretome has considerable potential for treating brain injuries. Previous studies have suggested that the effects of MSCs priming with exposure to hypoxia, cytokines, growth factors, or chemical agents could optimize the paracrine potency and therapeutic potential of MSCs. Studies have suggested that thrombin-primed Wharton's Jelly-derived mesenchymal stem cells (Th.WJ-MSCs) significantly enhance the neuroprotective beneficial effects of naive MSCs in brain injury such as hypoxic-ischemic brain injury (HIE) and intraventricular hemorrhage (IVH). This study aimed to characterize WJ-MSCs in terms of stem cell markers, differentiation, cell proliferation, and paracrine factors by comparing naive and Th.WJ-MSCs. We demonstrated that compared with naive MSCs, Th.MSCs significantly enhanced the neuroprotective effects in vitro. Moreover, we identified differentially expressed proteins in the conditioned media of naive and Th.WJ-MSCs by liquid chromatography-tandem mass spectrometry analysis. Secretome analysis of the conditioned medium of WJ-MSCs revealed that such neuroprotective effects were mediated by paracrine effects with secretomes of Th.WJ-MSCs, and hepatocyte growth factor was identified as a key paracrine mediator. These results can be applied further in the preclinical and clinical development of effective and safe cell therapeutics for brain injuries such as HIE and IVH.
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Affiliation(s)
- Geun-Hyoung Ha
- Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon, Republic of Korea
- Medical Innovation Technology, Inc. (MEDINNO, Inc.), Seoul, Republic of Korea
| | - Je Young Yeon
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Ki Hoon Kim
- Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon, Republic of Korea
- Medical Innovation Technology, Inc. (MEDINNO, Inc.), Seoul, Republic of Korea
| | - Du Man Lee
- Medical Innovation Technology, Inc. (MEDINNO, Inc.), Seoul, Republic of Korea
| | - Hye Yun Chae
- Medical Innovation Technology, Inc. (MEDINNO, Inc.), Seoul, Republic of Korea
| | - Hyun Nam
- Medical Innovation Technology, Inc. (MEDINNO, Inc.), Seoul, Republic of Korea
- Stem Cell and Regenerative Medicine Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea
- Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
| | - Kyunghoon Lee
- Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
- Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
| | - Dong Oh Kim
- Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
| | - Chung Kwon Kim
- Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon, Republic of Korea
- Medical Innovation Technology, Inc. (MEDINNO, Inc.), Seoul, Republic of Korea
| | - Kyeung Min Joo
- Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon, Republic of Korea
- Medical Innovation Technology, Inc. (MEDINNO, Inc.), Seoul, Republic of Korea
- Stem Cell and Regenerative Medicine Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea
- Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
- Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
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Hazrati P, Mirtaleb MH, Boroojeni HSH, Koma AAY, Nokhbatolfoghahaei H. Current Trends, Advances, and Challenges of Tissue Engineering-Based Approaches of Tooth Regeneration: A Review of the Literature. Curr Stem Cell Res Ther 2024; 19:473-496. [PMID: 35984017 DOI: 10.2174/1574888x17666220818103228] [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: 04/05/2022] [Revised: 05/17/2022] [Accepted: 06/01/2022] [Indexed: 11/22/2022]
Abstract
INTRODUCTION Tooth loss is a significant health issue. Currently, this situation is often treated with the use of synthetic materials such as implants and prostheses. However, these treatment modalities do not fully meet patients' biological and mechanical needs and have limited longevity. Regenerative medicine focuses on the restoration of patients' natural tissues via tissue engineering techniques instead of rehabilitating with artificial appliances. Therefore, a tissue-engineered tooth regeneration strategy seems like a promising option to treat tooth loss. OBJECTIVE This review aims to demonstrate recent advances in tooth regeneration strategies and discoveries about underlying mechanisms and pathways of tooth formation. RESULTS AND DISCUSSION Whole tooth regeneration, tooth root formation, and dentin-pulp organoid generation have been achieved by using different seed cells and various materials for scaffold production. Bioactive agents are critical elements for the induction of cells into odontoblast or ameloblast lineage. Some substantial pathways enrolled in tooth development have been figured out, helping researchers design their experiments more effectively and aligned with the natural process of tooth formation. CONCLUSION According to current knowledge, tooth regeneration is possible in case of proper selection of stem cells, appropriate design and manufacturing of a biocompatible scaffold, and meticulous application of bioactive agents for odontogenic induction. Understanding innate odontogenesis pathways play a crucial role in accurately planning regenerative therapeutic interventions in order to reproduce teeth.
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Affiliation(s)
- Parham Hazrati
- School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Helia Sadat Haeri Boroojeni
- Oral and Maxillofacial Surgery Department, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Hanieh Nokhbatolfoghahaei
- Dental Research Center, Research Institute of Dental Sciences, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Shah AA, Sheikh AA, Hasin D, Shah F, Aarif O, Shah RA, Ahmad SB, Maqbool S, Pampori ZA. Isolation, in vitro expansion and characterization of ovine fetal adnexa-derived mesenchymal stem cells reveals a source dependent trilineage differentiation and growth kinetics. Anim Biotechnol 2023; 34:3908-3919. [PMID: 37493347 DOI: 10.1080/10495398.2023.2238015] [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: 07/27/2023]
Abstract
This study was designed to isolate, cultivate, characterize and evaluate the growth kinetics of mesenchymal stem cells (MSCs) derived from fetal adnexa of sheep. The gravid uteri of ewes were collected from a local abattoir. The MSCs isolated from different fetal regions (Wharton's Jelly [oWJ], cord blood [oCB], amniotic fluid [oAF] and amniotic Sac [oAS]) were expanded in vitro and characterized for surface and pluripotency markers. The growth kinetics of MSCs was compared at 3rd and 5th passages. Similarly, the colony-forming efficiency (CFE) assay was performed at 3rd passage. The fetal adnexa-derived ovine MSCs showed the expression of CD73, CD90 and CD105. Similarly, the MSCs also expressed pluripotency markers, OCT4 and SOX2. Besides, cells also differentiated into osteogenic, chondrogenic and adipogenic lineages. The MSCs in culture showed a typical growth curve with initial lag phase, an exponential phase, a plateau phase and a decline phase. The growth rate was highest in oAF-MSCs at P5. The population doubling time (PDT) was highest in oAS-MSCs (87.28 ± 3.24 h), whereas the colony number was highest in oAF-MSCs (53.67 ± 4.06). The study reveals that oAF-MSCs were superior which outperformed other MSCs indicating that oAF-derived MSCs could be utilized for regenerative medicine.
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Affiliation(s)
- Aamir Amin Shah
- Division of Veterinary Physiology, Faculty of Veterinary Sciences and Animal Husbandry, SKUAST-Kashmir, Shuhama, J & K, India
| | - Aasif Ahmad Sheikh
- Division of Veterinary Physiology, Faculty of Veterinary Sciences and Animal Husbandry, SKUAST-Kashmir, Shuhama, J & K, India
| | - Dilruba Hasin
- Division of Veterinary Physiology, Faculty of Veterinary Sciences and Animal Husbandry, SKUAST-Kashmir, Shuhama, J & K, India
| | - Fozia Shah
- Division of Veterinary Physiology, Faculty of Veterinary Sciences and Animal Husbandry, SKUAST-Kashmir, Shuhama, J & K, India
| | - Ovais Aarif
- Division of Veterinary Physiology, Faculty of Veterinary Sciences and Animal Husbandry, SKUAST-Kashmir, Shuhama, J & K, India
| | - Riaz Ahmad Shah
- Division of Animal Biotechnology, Faculty of Veterinary Sciences and Animal Husbandry, SKUAST-Kashmir, Shuhama, J & K, India
| | - Sheikh Bilal Ahmad
- Division of Veterinary Biochemistry, Faculty of Veterinary Sciences and Animal Husbandry, SKUAST-Kashmir, Shuhama, J & K, India
| | - Showkat Maqbool
- Division of Animal Genetics and Breeding, Faculty of Veterinary Sciences and Animal Husbandry, SKUAST-Kashmir, Shuhama, J & K, India
| | - Z A Pampori
- Division of Veterinary Physiology, Faculty of Veterinary Sciences and Animal Husbandry, SKUAST-Kashmir, Shuhama, J & K, India
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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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Özkan B, Yılmaz Tuğan B, Hemşinlioğlu C, Sır Karakuş G, Şahin Ö, Ovalı E. Suprachoroidal spheroidal mesenchymal stem cell implantation in retinitis pigmentosa: clinical results of 6 months follow-up. Stem Cell Res Ther 2023; 14:252. [PMID: 37705097 PMCID: PMC10500760 DOI: 10.1186/s13287-023-03489-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Accepted: 09/04/2023] [Indexed: 09/15/2023] Open
Abstract
PURPOSE This prospective clinical case series aimed to evaluate the effect of suprachoroidal implantation of mesenchymal stem cells (MSCs) in the form of spheroids as a stem cell therapy for retinitis pigmentosa (RP) patients with relatively good visual acuity. METHODS Fifteen eyes of 15 patients with RP who received suprachoroidal implantation of MSCs in the form of spheroids were included. Best-corrected visual acuity (BCVA), 10-2 and 30-2 visual field examination and multifocal electroretinography (mfERG) recordings were recorded at baseline, postoperative 1st, 3rd and 6th months during follow-up. RESULTS Baseline median BCVA of RP patients was 1.30 (1.00-2.00) logMAR. BCVA has improved to 1.00 (0.50-1.30), 0.80 (0.40-1.30) and 0.80 (0.40-1.30) at the postoperative 1st, 3rd and 6th months, respectively. The improvements from baseline to the 3rd and 6th months were statistically significant (p = 0.03 and p < 0.001, respectively). In the 30-2 VF test, median MD was significantly improved at the 6th month compared to baseline (p = 0.030). In the 10-2 VF test, the median MD value was significantly different at the 6th month compared to the baseline (p = 0.043). The PSD value of the 10-2 VF test was significantly different at the 6th month compared to the 3rd month (p = 0.043). The amplitudes of P1 waves in < 2°, 5°-10° and 10°-15° rings improved significantly at the postoperative 6th month (p = 0.014, p = 0.018 and p = 0.017, respectively). There was also a statistically significant improvement in implicit times of P1 waves in 10°-15° ring at the postoperative 6th month (p = 0.004). CONCLUSION Suprachoroidal implantation of MSCs in the form of spheroids as a stem cell therapy for RP patients with relatively good visual acuity has an improving effect on BCVA, VF and mfERG recordings during the 6-month follow-up period. Spheroidal MSCs with enhanced effects may be more successful in preventing apoptosis and improving retinal tissue healing in RP patients.
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Affiliation(s)
- Berna Özkan
- Department of Ophthalmology, Acıbadem Mehmet Ali Aydınlar University, Istanbul, Turkey.
| | | | | | | | - Özlem Şahin
- Department of Ophthalmology, Marmara University, Istanbul, Turkey
| | - Ercüment Ovalı
- Acıbadem Labcell Cellular Therapy Center, Istanbul, Turkey
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Rebelatto CLK, Boldrini-Leite LM, Daga DR, Marsaro DB, Vaz IM, Jamur VR, de Aguiar AM, Vieira TB, Furman BP, Aguiar CO, Brofman PRS. Quality Control Optimization for Minimizing Security Risks Associated with Mesenchymal Stromal Cell-Based Product Development. Int J Mol Sci 2023; 24:12955. [PMID: 37629136 PMCID: PMC10455270 DOI: 10.3390/ijms241612955] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 08/09/2023] [Accepted: 08/15/2023] [Indexed: 08/27/2023] Open
Abstract
Mesenchymal stromal cells (MSCs) have been considered a therapeutic strategy in regenerative medicine because of their regenerative and immunomodulatory properties. The translation of MSC-based products has some challenges, such as regulatory and scientific issues. Quality control should be standardized and optimized to guarantee the reproducibility, safety, and efficacy of MSC-based products to be administered to patients. The aim of this study was to develop MSC-based products for use in clinical practice. Quality control assays include cell characterization, cell viability, immunogenicity, and cell differentiation; safety tests such as procoagulant tissue factor (TF), microbiological, mycoplasma, endotoxin, genomic stability, and tumorigenicity tests; and potency tests. The results confirm that the cells express MSC markers; an average cell viability of 96.9%; a low expression of HLA-DR and costimulatory molecules; differentiation potential; a high expression of TF/CD142; an absence of pathogenic microorganisms; negative endotoxins; an absence of chromosomal abnormalities; an absence of genotoxicity and tumorigenicity; and T-lymphocyte proliferation inhibition potential. This study shows the relevance of standardizing the manufacturing process and quality controls to reduce variability due to the heterogeneity between donors. The results might also be useful for the implementation and optimization of new analytical techniques and automated methods to improve safety, which are the major concerns related to MSC-based therapy.
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Affiliation(s)
- Carmen Lúcia Kuniyoshi Rebelatto
- Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.)
- National Institute of Science and Technology for Regenerative Medicine—INCT-REGENERA, Rio de Janeiro 21941-599, Brazil
| | - Lidiane Maria Boldrini-Leite
- Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.)
- National Institute of Science and Technology for Regenerative Medicine—INCT-REGENERA, Rio de Janeiro 21941-599, Brazil
| | - Debora Regina Daga
- Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.)
- National Institute of Science and Technology for Regenerative Medicine—INCT-REGENERA, Rio de Janeiro 21941-599, Brazil
| | - Daniela Boscaro Marsaro
- Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.)
- National Institute of Science and Technology for Regenerative Medicine—INCT-REGENERA, Rio de Janeiro 21941-599, Brazil
| | - Isadora May Vaz
- Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.)
- National Institute of Science and Technology for Regenerative Medicine—INCT-REGENERA, Rio de Janeiro 21941-599, Brazil
| | - Valderez Ravaglio Jamur
- Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.)
- National Institute of Science and Technology for Regenerative Medicine—INCT-REGENERA, Rio de Janeiro 21941-599, Brazil
| | - Alessandra Melo de Aguiar
- Laboratory of Basic Biology of Stem Cells, Carlos Chagas Institute—Fiocruz-Paraná, Curitiba 81350-010, Brazil;
| | - Thalita Bastida Vieira
- Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.)
| | - Bianca Polak Furman
- Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.)
| | - Cecília Oliveira Aguiar
- Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.)
| | - Paulo Roberto Slud Brofman
- Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Brazil; (L.M.B.-L.); (D.R.D.); (D.B.M.); (I.M.V.); (V.R.J.); (T.B.V.); (B.P.F.); (C.O.A.); (P.R.S.B.)
- National Institute of Science and Technology for Regenerative Medicine—INCT-REGENERA, Rio de Janeiro 21941-599, Brazil
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Stefańska K, Nemcova L, Blatkiewicz M, Żok A, Kaczmarek M, Pieńkowski W, Mozdziak P, Piotrowska-Kempisty H, Kempisty B. Expression Profile of New Marker Genes Involved in Differentiation of Human Wharton's Jelly-Derived Mesenchymal Stem Cells into Chondrocytes, Osteoblasts, Adipocytes and Neural-like Cells. Int J Mol Sci 2023; 24:12939. [PMID: 37629120 PMCID: PMC10455417 DOI: 10.3390/ijms241612939] [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: 07/17/2023] [Revised: 08/10/2023] [Accepted: 08/17/2023] [Indexed: 08/27/2023] Open
Abstract
Wharton's jelly (WJ) contains mesenchymal stem cells (MSCs) exhibiting broad immunomodulatory properties and differentiation capacity, which makes them a promising tool for cellular therapies. Although the osteogenic, chondrogenic and adipogenic differentiation is a gold standard for proper identification of MSCs, it is important to elucidate the exact molecular mechanisms governing these processes to develop safe and efficient cellular therapies. Umbilical cords were collected from healthy, full-term deliveries, for subsequent MSCs (WJ-MSCs) isolation. WJ-MSCs were cultivated in vitro for osteogenic, chondrogenic, adipogenic and neurogenic differentiation. The RNA samples were isolated and the transcript levels were evaluated using NovaSeq platform, which led to the identification of differentially expressed genes. Expression of H19 and SLPI was enhanced in adipocytes, chondrocytes and osteoblasts, and NPPB was decreased in all analyzed groups compared to the control. KISS1 was down-regulated in adipocytes, chondrocytes, and neural-like cells compared to the control. The most of identified genes were already implicated in differentiation of MSCs; however, some genes (PROK1, OCA2) have not yet been associated with initiating final cell fate. The current results indicate that both osteo- and adipo-induced WJ-MSCs share many similarities regarding the most overexpressed genes, while the neuro-induced WJ-MSCs are quite distinctive from the other three groups. Overall, this study provides an insight into the transcriptomic changes occurring during the differentiation of WJ-MSCs and enables the identification of novel markers involved in this process, which may serve as a reference for further research exploring the role of these genes in physiology of WJ-MSCs and in regenerative medicine.
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Affiliation(s)
- Katarzyna Stefańska
- Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland
- Cellivia 3 S.A., 61-623 Poznan, Poland
| | - Lucie Nemcova
- Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, 27721 Libechov, Czech Republic
| | - Małgorzata Blatkiewicz
- Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland
| | - Agnieszka Żok
- Division of Philosophy of Medicine and Bioethics, Poznan University of Medical Sciences, 60-806 Poznan, Poland
| | - Mariusz Kaczmarek
- Department of Cancer Immunology, Poznan University of Medical Sciences, 61-866 Poznan, Poland
- Gene Therapy Laboratory, Department of Cancer Diagnostics and Immunology, Greater Poland Cancer Centre, 61-866 Poznan, Poland
| | - Wojciech Pieńkowski
- Division of Perinatology and Women’s Diseases, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Paul Mozdziak
- Prestage Department of Poultry Sciences, North Carolina State University, Raleigh, NC 27695, USA
| | - Hanna Piotrowska-Kempisty
- Department of Toxicology, Poznan University of Medical Sciences, 60-631 Poznan, Poland
- Department of Basic and Preclinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland
| | - Bartosz Kempisty
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland
- Division of Anatomy, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland
- Department of Obstetrics and Gynecology, University Hospital and Masaryk University, 60177 Brno, Czech Republic
- Physiology Graduate Faculty, North Carolina State University, Raleigh, NC 27695, USA
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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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20
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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: 3] [Impact Index Per Article: 1.5] [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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21
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Chen P, Tang S, Li M, Wang D, Chen C, Qiu Y, Fang Z, Zhang H, Gao H, Weng H, Hu K, Lin J, Lin Q, Tan Y, Li S, Chen J, Chen L, Chen X. Single-Cell and Spatial Transcriptomics Decodes Wharton's Jelly-Derived Mesenchymal Stem Cells Heterogeneity and a Subpopulation with Wound Repair Signatures. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2204786. [PMID: 36504438 PMCID: PMC9896049 DOI: 10.1002/advs.202204786] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 11/18/2022] [Indexed: 06/17/2023]
Abstract
The highly heterogeneous characteristics of Wharton's jelly mesenchymal stem cells (WJ-MSCs) may be responsible for the poor clinical outcomes and poor reproducibility of treatments based on WJ-MSCs. Exploration of WJ-MSC heterogeneity with multimodal single-cell technologies will aid in establishing accurate MSC subtyping and developing screening protocols for dominant functional subpopulations. Here, the characteristics of WJ-MSCs are systematically analyzed by single cell and spatial transcriptome sequencing. Single-cell transcriptomics analysis identifies four WJ-MSC subpopulations, namely proliferative_MSCs, niche-supporting_MSCs, metabolism-related_MSCs and biofunctional-type_MSCs. Furthermore, the transcriptome, cellular heterogeneity, and cell-state trajectories of these subpopulations are characterized. Intriguingly, the biofunctional-type MSCs (marked by S100A9, CD29, and CD142) selected in this study exhibit promising wound repair properties in vitro and in vivo. Finally, by integrating omics data, it has been found that the S100A9+ CD29+ CD142+ subpopulation is more enriched in the fetal segment of the umbilical cord, suggesting that this subpopulation deriving from the fetal segment may have potential for developing into an ideal therapeutic agent for wound healing. Overall, the presented study comprehensively maps the heterogeneity of WJ-MSCs and provides an essential resource for future development of WJ-MSC-based drugs.
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22
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da Silva CG, Martins CF. Stem Cells as Nuclear Donors for Mammalian Cloning. Methods Mol Biol 2023; 2647:105-119. [PMID: 37041331 DOI: 10.1007/978-1-0716-3064-8_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/13/2023]
Abstract
Mammals are routinely cloned by introducing somatic nuclei into enucleated oocytes. Cloning contributes to propagating desired animals, to germplasm conservation efforts, among other applications. A challenge to more broader use of this technology is the relatively low cloning efficiency, which inversely correlates with donor cell differentiation status. Emerging evidence suggests that adult multipotent stem cells improve cloning efficiency, while the greater potential of embryonic stem cells for cloning remains restricted to the mouse. The derivation of pluripotent or totipotent stem cells from livestock and wild species and their association with modulators of epigenetic marks in donor cells should increase cloning efficiency.
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Affiliation(s)
- Carolina Gonzales da Silva
- Federal Institute of Education, Science and Technology of Bahia, Campus Xique-Xique, Xique-Xique, Bahia, Brazil
| | - Carlos Frederico Martins
- Brazilian Agricultural Research Corporation (Embrapa Cerrados), Brasília, Federal District, Brazil.
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23
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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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24
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Zhang C, Huang L, Wang X, Zhou X, Zhang X, Li L, Wu J, Kou M, Cai C, Lian Q, Zhou X. Topical and intravenous administration of human umbilical cord mesenchymal stem cells in patients with diabetic foot ulcer and peripheral arterial disease: a phase I pilot study with a 3-year follow-up. Stem Cell Res Ther 2022; 13:451. [PMID: 36064461 PMCID: PMC9446755 DOI: 10.1186/s13287-022-03143-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 08/16/2022] [Indexed: 12/26/2022] Open
Abstract
Background Diabetic foot ulcer (DFU) is a serious chronic complication of diabetes mellitus that contributes to 85% of nontraumatic lower extremity amputations in diabetic patients. Preliminary clinical benefits have been shown in treatments based on mesenchymal stem cells for patients with DFU or peripheral arterial disease (PAD). However, the long-term safety and benefits are unclear for patients with both DFU and PAD who are not amenable to surgical revascularization. Methods In this phase I pilot study, 14 patients with PAD and incurable DFU were enrolled to assess the safety and efficacy of human umbilical cord mesenchymal stem cell (hUC-MSC) administration based on conservative treatments. All patients received topical and intravenous administrations of hUC-MSCs at a dosage of 2 × 105 cells/kg with an upper limit of 1 × 107 cells for each dose. The adverse events during treatment and follow-up were documented for safety assessments. The therapeutic efficacy was assessed by ulcer healing status, recurrence rate, and 3-year amputation-free rate in the follow-up phase. Results The safety profiles were favorable. Only 2 cases of transient fever were observed within 3 days after transfusion and considered possibly related to hUC-MSC administration intravenously. Ulcer disclosure was achieved for more than 95% of the lesion area for all patients within 1.5 months after treatment. The symptoms of chronic limb ischaemia were alleviated along with a decrease in Wagner scores, Rutherford grades, and visual analogue scale scores. No direct evidence was observed to indicate the alleviation of the obstruction in the main vessels of target limbs based on computed tomography angiography. The duration of rehospitalization for DFU was 2.0 ± 0.6 years. All of the patients survived without amputation due to the recurrence of DFU within 3 years after treatments. Conclusions Based on the current pilot study, the preliminary clinical benefits of hUC-MSCs on DFU healing were shown, including good tolerance, a shortened healing time to 1.5 months and a favorable 3-year amputation-free survival rate. The clinical evidence in the current study suggested a further phase I/II study with a larger patient population and a more rigorous design to explore the efficacy and mechanism of hUC-MSCs on DFU healing. Trial registration: The current study was registered retrospectively on 22 Jan 2022 with the Chinese Clinical Trial Registry (ChiCTR2200055885), http://www.chictr.org.cn/showproj.aspx?proj=135888 Graphical Abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-03143-0.
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Affiliation(s)
- Che Zhang
- Department of Pediatrics, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.,Clinical Research Centre, Affiliated Taihe Hospital of Hubei University of Medicine, Shiyan, China
| | - Li Huang
- Clinical Research Centre, Affiliated Taihe Hospital of Hubei University of Medicine, Shiyan, China.,Guangzhou Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China
| | - Xiaofen Wang
- Department of Endocrinology, Affiliated Taihe Hospital of Hubei University of Medicine, Shiyan, China
| | - Xiaoya Zhou
- Guangzhou Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China
| | - Xiaoxian Zhang
- Guangzhou Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China
| | - Ling Li
- Clinical Data Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Jieying Wu
- Guangzhou Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China
| | - Meng Kou
- Guangzhou Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China
| | - Cheguo Cai
- Shenzhen Beike Biotechnology Co., Ltd., Shenzhen, China
| | - Qizhou Lian
- Guangzhou Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China. .,Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
| | - Xihui Zhou
- Department of Pediatrics, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.
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25
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Wu Y, Zheng Y, Jin Z, Li S, Wu W, An C, Guo J, Zhu Z, Zhou T, Zhou Y, Cen L. Controllable manipulation of alginate-gelatin core-shell microcarriers for HUMSCs expansion. Int J Biol Macromol 2022; 216:1-13. [PMID: 35777503 DOI: 10.1016/j.ijbiomac.2022.06.173] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 06/20/2022] [Accepted: 06/26/2022] [Indexed: 11/29/2022]
Abstract
Human umbilical cord mesenchymal stem cells (HUMSCs) are one of the most attractive sources of stem cells, and it is meaningful to design and develop a type of microcarriers with suitable mechanical strength for HUMSCs proliferation in order to acquire enough cells for cell-based therapy. Alginate-gelatin core-shell (AG) soft microcarriers were thus fabricated via a microfluidic device with droplet shearing/gelation facilities and surface coating for in vitro expansion of HUMSCs. The attachment and proliferation of HUMSCs on AG microcarriers with different mechanical strengths modulated by gelatin coating was studied, and the harvested cells were characterized to verity their differentiation potential. The obtained core-shell microcarriers were all uniform in size with a high mono-dispersity (CV < 5 %). An increase in the gelatin surface coating concentration from 0.5 % to 1.5 % would lead to the reduction in both the particle size of the microcarriers and swelling ratio upon the contact of culture medium, but increased elastic modulus. Microcarriers of 245.12 μm with a gelatin coating elastic modulus of 27.5 kPa (AG10) were found to be the optimal substrate for HUMSCs with an initial attachment efficiency of 44.41 % and a 5-day expansion efficiency of 647 %. The cells harvested from AG10 still reserved their outstanding pluripotency. Fresh AG10 could smoothly transfer cells from a running microcarrier-cell system of confluence to serve as a convenient way of scaling-up the existing culture. The current study thus developed suitable microcarriers, AG10, for in vitro HUMSCs expansion with well reserve of cell multipotency, and also provided a manufacturing and surface manipulating strategy of precise production and fine regulation of microcarrier properties.
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Affiliation(s)
- Yanfei Wu
- Shanghai Key Laboratory of Multiphase Materials Chemical Engineering, Department of Product Engineering, School of Chemical Engineering, East China University of Science and Technology, No.130 Mei Long Road, Shanghai 200237, China
| | - Yiling Zheng
- Shanghai Key Laboratory of Multiphase Materials Chemical Engineering, Department of Product Engineering, School of Chemical Engineering, East China University of Science and Technology, No.130 Mei Long Road, Shanghai 200237, China
| | - Ziyang Jin
- State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, No.130 Mei Long Road, Shanghai 200237, China
| | - Shihao Li
- State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, No.130 Mei Long Road, Shanghai 200237, China
| | - Weiqian Wu
- Shanghai Key Laboratory of Multiphase Materials Chemical Engineering, Department of Product Engineering, School of Chemical Engineering, East China University of Science and Technology, No.130 Mei Long Road, Shanghai 200237, China
| | - Chenjing An
- Shanghai Key Laboratory of Multiphase Materials Chemical Engineering, Department of Product Engineering, School of Chemical Engineering, East China University of Science and Technology, No.130 Mei Long Road, Shanghai 200237, China
| | - Jiahao Guo
- Shanghai Key Laboratory of Multiphase Materials Chemical Engineering, Department of Product Engineering, School of Chemical Engineering, East China University of Science and Technology, No.130 Mei Long Road, Shanghai 200237, China
| | - Zhihua Zhu
- Shanghai Key Laboratory of Multiphase Materials Chemical Engineering, Department of Product Engineering, School of Chemical Engineering, East China University of Science and Technology, No.130 Mei Long Road, Shanghai 200237, China
| | - Tian Zhou
- Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China..
| | - Yan Zhou
- State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, No.130 Mei Long Road, Shanghai 200237, China..
| | - Lian Cen
- Shanghai Key Laboratory of Multiphase Materials Chemical Engineering, Department of Product Engineering, School of Chemical Engineering, East China University of Science and Technology, No.130 Mei Long Road, Shanghai 200237, China.
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26
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Coccini T, Spinillo A, Roccio M, Lenta E, Valsecchi C, De Simone U. Human Umbilical Cord Mesenchymal Stem Cell-Based in vitro Model for Neurotoxicity Testing. Curr Protoc 2022; 2:e423. [PMID: 35471597 DOI: 10.1002/cpz1.423] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Neurotoxicity (NT) testing for regulatory purposes is based on in vivo animal testing. There is general consensus, however, about the need for the development of alternative methodologies to allow researchers to more rapidly and cost effectively screen large numbers of chemicals for their potential to cause NT, or to investigate their mode of action. In vitro assays are considered an important source of information for making regulatory decisions, and human cell-based systems are recommended as one of the most relevant models in toxicity testing, to reduce uncertainty in the extrapolation of results from animal-based models. Human neuronal models range from various neuroblastoma cell lines to stem cell-derived systems, including those derived from mesenchymal stem/stromal cells (hMSC). hMSCs exhibit numerous advantages, including the fact that they can be obtained in high yield from healthy human adult tissues, can be cultured with a minimal laboratory setup and without genetic manipulations, are able of continuous and repeated self-renewal, are nontumorigenic, and can form large populations of stably differentiated cells representative of different tissues, including neuronal cells. hMSCs derived from human umbilical cord (hUC) in particular possess several prominent advantages, including a painless, non-invasive, and ethically acceptable collection procedure, simple and convenient preparation, and high proliferation capacity. In addition, hMSCs can be efficiently differentiated into neuron-like cells (hNLCs), which can then be used for the assessment of neuronal toxicity of potential neurotoxic compounds in humans. Here, we describe a step-by-step procedure to use hMSCs from the umbilical cord for in vitro neurotoxicity testing. First, we describe how to isolate, amplify, and store hMSCs derived from the umbilical cord. We then outline the steps to transdifferentiate these cells into hNLCs, and then use the hNLCs for neurotoxicity testing by employing multiple common cytotoxicity assays after treatment with test compounds. The approach follows the most updated guidance on using human cell-based systems. These protocols will allow investigators to implement an alternative system for obtaining primary NLCs of human origin, and support advancement in neurotoxicity research. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Isolation and maintenance of human mesenchymal stem/stromal cells (hMSCs) obtained from the umbilical cord lining membrane Basic Protocol 2: Transdifferentiation of hMSCs into neuron-like cells (hNLCs) and basic neurotoxicity assessment.
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Affiliation(s)
- Teresa Coccini
- Laboratory of Clinical and Experimental Toxicology, and Pavia Poison Centre-National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Arsenio Spinillo
- Department of Obstetrics and Gynecology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Marianna Roccio
- Department of Obstetrics and Gynecology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Elisa Lenta
- Immunology and Transplantation Laboratory, Pediatric Hematology Oncology Unit, Cell Factory, Department of Maternal and Children's Health, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Chiara Valsecchi
- Immunology and Transplantation Laboratory, Pediatric Hematology Oncology Unit, Cell Factory, Department of Maternal and Children's Health, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Uliana De Simone
- Laboratory of Clinical and Experimental Toxicology, and Pavia Poison Centre-National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
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Anudeep TC, Jeyaraman M, Muthu S, Rajendran RL, Gangadaran P, Mishra PC, Sharma S, Jha SK, Ahn BC. Advancing Regenerative Cellular Therapies in Non-Scarring Alopecia. Pharmaceutics 2022; 14:pharmaceutics14030612. [PMID: 35335987 PMCID: PMC8953616 DOI: 10.3390/pharmaceutics14030612] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 02/28/2022] [Accepted: 03/07/2022] [Indexed: 02/05/2023] Open
Abstract
Alopecia or baldness is a common diagnosis in clinical practice. Alopecia can be scarring or non-scarring, diffuse or patchy. The most prevalent type of alopecia is non-scarring alopecia, with the majority of cases being androgenetic alopecia (AGA) or alopecia areata (AA). AGA is traditionally treated with minoxidil and finasteride, while AA is treated with immune modulators; however, both treatments have significant downsides. These drawbacks compel us to explore regenerative therapies that are relatively devoid of adverse effects. A thorough literature review was conducted to explore the existing proven and experimental regenerative treatment modalities in non-scarring alopecia. Multiple treatment options compelled us to classify them into growth factor-rich and stem cell-rich. The growth factor-rich group included platelet-rich plasma, stem cell-conditioned medium, exosomes and placental extract whereas adult stem cells (adipose-derived stem cell-nano fat and stromal vascular fraction; bone marrow stem cell and hair follicle stem cells) and perinatal stem cells (umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs), Wharton jelly-derived MSCs (WJ-MSCs), amniotic fluid-derived MSCs (AF-MSCs), and placental MSCs) were grouped into the stem cell-rich group. Because of its regenerative and proliferative capabilities, MSC lies at the heart of regenerative cellular treatment for hair restoration. A literature review revealed that both adult and perinatal MSCs are successful as a mesotherapy for hair regrowth. However, there is a lack of standardization in terms of preparation, dose, and route of administration. To better understand the source and mode of action of regenerative cellular therapies in hair restoration, we have proposed the "À La Mode Classification". In addition, available evidence-based cellular treatments for hair regrowth have been thoroughly described.
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Affiliation(s)
- Talagavadi Channaiah Anudeep
- Department of Plastic Surgery, Topiwala National Medical College and BYL Nair Ch. Hospital, Mumbai 400008, India;
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, India; (M.J.); (S.M.); (S.K.J.)
- À La Mode Esthétique Studio, Mysuru 570011, India
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi 110092, India; (P.C.M.); (S.S.)
| | - Madhan Jeyaraman
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, India; (M.J.); (S.M.); (S.K.J.)
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi 110092, India; (P.C.M.); (S.S.)
- Department of Orthopaedics, Faculty of Medicine—Sri Lalithambigai Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600095, India
| | - Sathish Muthu
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, India; (M.J.); (S.M.); (S.K.J.)
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi 110092, India; (P.C.M.); (S.S.)
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul 624304, India
| | - Ramya Lakshmi Rajendran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea;
| | - Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea;
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Korea
- Correspondence: (P.G.); (B.-C.A.)
| | - Prabhu Chandra Mishra
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi 110092, India; (P.C.M.); (S.S.)
| | - Shilpa Sharma
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi 110092, India; (P.C.M.); (S.S.)
- Department of Paediatric Surgery, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Saurabh Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, India; (M.J.); (S.M.); (S.K.J.)
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi 110092, India; (P.C.M.); (S.S.)
| | - Byeong-Cheol Ahn
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea;
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Korea
- Correspondence: (P.G.); (B.-C.A.)
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Kheirjou R, Rad JS, Khosroshahi AF, Davaran S, Roshangar L. Evaluation the ability of acellular ovine small intestine submucosa to load and release of mineral pitch and its anti-inflammatory effects. Cell Tissue Bank 2022; 23:541-555. [PMID: 35083606 DOI: 10.1007/s10561-021-09985-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Accepted: 11/28/2021] [Indexed: 11/26/2022]
Abstract
Injury from the severe burn is exacerbated by a persistent inflammatory response. This response is mediated by cytokines and chemokines, which are released from various immune cells, including mast cells. In this study, the ability of the acellular ovine small intestine submucosa (AOSIS) to load and release of Mineral Pitch (MP) was first investigated, and it was found that the preparation of the scaffold by a modified method enables it to load and release water-soluble drugs. Then, 32 male Wistar rats were divided into four groups, a third-degree burn was created, and except for the control group, the others were treated with: AOSIS, WJ-MSCs seeded AOSIS, or AOSIS loaded with WJ-MSCs and MP. Wound sampling on the 5th day after treatment showed that the number of intact and degranulated mast cells in the treatment groups was associated with a decrease compared to the control group. In the last group, this decrease was the largest (and statically significant (p < 0.05)). Also, by measuring the level of inflammatory factors in blood serum, it was found that in the treatment groups compared to the control group, IL-10 was associated with an increase, and TNF-α was associated with a decrease. The changes in inflammatory factors were more significant (p < 0.05) in the last group. So, our results indicate that AOSIS loaded with WJ-MSCs and MP could be used as an innovative tissue-engineered device to control inflammatory condition during burn wound healing.
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Affiliation(s)
- Raziyeh Kheirjou
- Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Jafar Soleimani Rad
- Stem Cell Research Center, Tabriz University of Medical Sciences, Golgasht Street, 51376563833, Tabriz, Iran
| | - Ahad Ferdowsi Khosroshahi
- Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Soodabeh Davaran
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Leila Roshangar
- Stem Cell Research Center, Tabriz University of Medical Sciences, Golgasht Street, 51376563833, Tabriz, Iran.
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Panero AJ, Hirahara AM, Podesta L, Jamali AA, Andersen W, Smith AA. Allograft Tissues. ATLAS OF INTERVENTIONAL ORTHOPEDICS PROCEDURES 2022:89-101. [DOI: 10.1016/b978-0-323-75514-6.00008-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Luo S, Xiao S, Ai Y, Wang B, Wang Y. Changes in the hepatic differentiation potential of human mesenchymal stem cells aged in vitro. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1628. [PMID: 34926672 PMCID: PMC8640908 DOI: 10.21037/atm-21-4918] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 10/13/2021] [Indexed: 11/15/2022]
Abstract
Background Due to their multipotency and ability for self-renewal, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) hold great promise for generating hepatocytes. Previous research has successfully generated hepatocytes from early-passage [i.e., passage (P)3] hUC-MSCs; however, the populations of early-passage cells are limited, and these cells cannot produce sufficient functional hepatocytes for large-scale application in clinical therapy. Thus, a thorough investigation of the hepatic differentiation potential of in vitro-aged hUC-MSCs is needed. Methods hUC-MSCs were passaged in vitro and subcultured every 3 days up to P8, and their morphology, proliferative capacity, liver-specific marker expression, and liver function at the end of each passage were analyzed. The efficiency of the hepatogenic differentiation of hUC-MSCs driven by a functional hit 1 (FH1)-based strategy at different passages was also evaluated. Results The in vitro-aged hUC-MSCs gradually displayed morphological inhomogeneity, had reduced proliferative capability, and exhibited senescent properties while maintaining adipogenic and osteogenic differentiation potential. Additionally, senescence also decreased the expression of messenger RNA (mRNA) levels in albumin (ALB) and alpha 1-antitrpsin (A1AT) in these cells and their relative protein expression, which is the marker of a mature hepatocyte. The liver function of the in vitro-aged hUC-MSCs also deteriorated gradually. Finally, the percentage of hepatocyte-like cells (HLCs) generated from in vitro-aged hUC-MSCs reduced significantly, and the mature hepatocyte functions, such as ALB secretion, glycogen synthesis, low-density lipoprotein (LDL) intake, and indocyanine green (ICG) uptake, also changed. Conclusions hUC-MSCs possess mature hepatocytes’ specific markers and functions, which change gradually as they undergo cell senescence. Due to the loss of these properties within in vitro subcultures, the hepatic differentiation efficiency of in vitro-aged hUC-MSCs decreased dramatically in the late passage (P8). The current study provides valuable information can inform future research on liver disease.
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Affiliation(s)
- Sang Luo
- State Key Laboratory of Virology, School of Life Sciences, Wuhan University, Wuhan, China
| | - Shuai Xiao
- State Key Laboratory of Virology, School of Life Sciences, Wuhan University, Wuhan, China
| | - Yang Ai
- State Key Laboratory of Virology, School of Life Sciences, Wuhan University, Wuhan, China
| | - Ben Wang
- State Key Laboratory of Virology, School of Life Sciences, Wuhan University, Wuhan, China
| | - Yefu Wang
- State Key Laboratory of Virology, School of Life Sciences, Wuhan University, Wuhan, China
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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: 30] [Impact Index Per Article: 7.5] [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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Guenther R, Dreschers S, Maassen J, Reibert D, Skazik-Voogt C, Gutermuth A. The Treasury of Wharton's Jelly. Stem Cell Rev Rep 2021; 18:1627-1638. [PMID: 34647276 PMCID: PMC9209346 DOI: 10.1007/s12015-021-10217-8] [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] [Accepted: 06/25/2021] [Indexed: 11/11/2022]
Abstract
Background Postnatal umbilical cord tissue contains valuable mesenchymal progenitor cells of various differentiation stages. While mesenchymal stem cells are plastic-adherent and tend to differentiate into myofibroblastic phenotypes, some round cells detach, float above the adherent cells, and build up cell aggregates, or form spheroids spontaneously. Very small luminescent cells are always involved as single cells or within collective forms and resemble the common well-known very small embryonic-like cells (VSELs). In this study, we investigated these VSELs-like cells in terms of their pluripotency phenotype and tri-lineage differentiation potential. Methods VSELs-like cells were isolated from cell-culture supernatants by a process that combines filtering, up concentration, and centrifugation. To determine their pluripotency character, we measured the expression of Nanog, Sox-2, Oct-4, SSEA-1, CXCR4, SSEA-4 on gene and protein level. In addition, the cultured cells derived from UC tissue were examined regarding their potential to differentiate into three germ layers. Result The VSELs-like cells express all of the pluripotency-associated markers we investigated and are able to differentiate into meso- endo- and ectodermal precursor cells. Conclusions Umbilical cord tissue hosts highly potent VSELs-like stem cells. Graphical Abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1007/s12015-021-10217-8.
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Affiliation(s)
- Rebecca Guenther
- Department for Applied Cell Biology, Fraunhofer Institute for Production Technology, Steinbachstr. 17, 52074, Aachen, Germany
| | - Stephan Dreschers
- Clinic for Gynaecology, University Hospital Aachen, Pauwelsstr 30, 52074, Aachen, Germany
| | - Jessika Maassen
- Department for Applied Cell Biology, Fraunhofer Institute for Production Technology, Steinbachstr. 17, 52074, Aachen, Germany
| | - Daniel Reibert
- Department for Applied Cell Biology, Fraunhofer Institute for Production Technology, Steinbachstr. 17, 52074, Aachen, Germany
| | - Claudia Skazik-Voogt
- Department for Applied Cell Biology, Fraunhofer Institute for Production Technology, Steinbachstr. 17, 52074, Aachen, Germany
| | - Angela Gutermuth
- Department for Applied Cell Biology, Fraunhofer Institute for Production Technology, Steinbachstr. 17, 52074, Aachen, Germany.
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Lv X, Wang L, Zou X, Huang S. Umbilical Cord Mesenchymal Stem Cell Therapy for Regenerative Treatment of Rheumatoid Arthritis: Opportunities and Challenges. DRUG DESIGN DEVELOPMENT AND THERAPY 2021; 15:3927-3936. [PMID: 34584402 PMCID: PMC8462093 DOI: 10.2147/dddt.s323107] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 08/26/2021] [Indexed: 12/25/2022]
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology with a high rate of disability. Traditional treatments for RA remain a challenging issue. For example, nonsteroidal anti-inflammatory drugs (NSAIDs) have no therapeutic effects on joint destruction, and the prominent side effects include gastrointestinal symptoms. RA is characterized by recurrence and bone attrition. Therefore, regenerative medicine and the use of umbilical cord mesenchymal stem cell (UC-MSC) therapies have recently emerged as potential options. UC-MSCs are multifunctional stem cells that are present in neonatal umbilical cord tissue and can differentiate into many kinds of cells, which have broad clinical application prospects in the tissue engineering of bone, cartilage, muscle, tendon, ligament, nerve, liver, endothelium, and myocardium. Moreover, UC-MSCs have advantages, such as convenient collection of materials and no ethical disputes; thus, these cells have attracted increasing attention from researchers. However, there are few clinical studies regarding UC-MSC therapy for RA. In this paper, we will review traditional drugs for RA treatment and then focus on UC-MSC therapy for RA, including preclinical and clinical UC-MSC applications for RA patients in the context of regenerative medicine. Finally, we will summarize the challenges and perspectives of UC-MSCs as a potential therapeutic strategy for RA. This review will help to design and discover more potent and efficacious treatments for RA patients and aid in advancing this class of cell therapy.
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Affiliation(s)
- Xiaolan Lv
- Department of Laboratory Medicine, Liuzhou Maternity and Child Healthcare Hospital, Liu Zhou, Guang Xi, People's Republic of China
| | - Liming Wang
- Shaanxi Jiuzhou Biomedical Science and Technology Group, Xi'an, Shaan Xi, People's Republic of China
| | - XiaoRong Zou
- Department of Hematology, 986 Hospital of Fourth Military Medical University, Xi'an, Shaan Xi, People's Republic of China
| | - Shigao Huang
- Faculty of Health Sciences, University of Macau, Macau, People's Republic of China
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Microrna analysis of human decidua mesenchymal stromal cells from preeclampsia patients. Placenta 2021; 115:12-19. [PMID: 34534911 DOI: 10.1016/j.placenta.2021.09.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 09/06/2021] [Accepted: 09/07/2021] [Indexed: 01/03/2023]
Abstract
INTRODUCTION In preeclampsia (PE), human decidua mesenchymal stromal cells (hDMSCs) are exposed to abnormally high levels of oxidative stress and inflammatory factors circulating in the maternal blood. MicroRNAs (miRNAs) have been shown to have a significant impact on the differentiation, maturation and function of mesenchymal stromal cells (MSCs). Our aim in the present study is firstly to investigate differentially expressed miRNA levels to be used as a biomarker in the early detection of PE and secondly to investigate whether those differentially expressed miRNAs in hDMSCs have an effect on the pathogenesis of PE. METHODS This study covers miRNA expression analysis of hDMSCs from 7 PE patient and 7 healthy pregnant women and is a preliminary study to investigate putative biomarkers. After cell culture and cell sorting, total RNA including miRNAs were isolated from hDMSCs. Let-7b-3p, let-7f-1-3p, miR-191-3p, miR-550a-5p, miR-33b-3p and miR-425-3p were used for miRNA analysis and U6 snRNA was used for normalization of the samples. MiRNA analysis was performed by droplet digital polymerase chain reaction (ddPCR) method and obtained results were evaluated statistically. RESULTS As a result of the analysis, it was observed that the levels of hsa-miR-33b-3p significantly (AUC: 0.93, p = 0.04, fold change: 4.5) increased in hDMSC of PE patients compared to healthy controls. However, let-7b-3p, let-7f-1-3p, miR-191-3p, miR-550a-5p, and miR-425-3p were not considered as significant because they did not meet the p < 0,05 requirement. DISCUSSION Within the scope of the study, it is predicted that miR-33b-3p (p = 0.004, AUC = 0.93) can be used as a biomarker in detecting PE.
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Luo S, Ai Y, Xiao S, Wang B, Wang Y. Functional hit 1 (FH1)-based rapid and efficient generation of functional hepatocytes from human mesenchymal stem cells: a novel strategy for hepatic differentiation. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1087. [PMID: 34422999 PMCID: PMC8339809 DOI: 10.21037/atm-21-2829] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 06/25/2021] [Indexed: 12/19/2022]
Abstract
Background Because the liver is central to the physiology of the body, primary hepatocytes are widely used in liver pathology and physiological research, such as liver drug screening, bioartificial liver support system, and cell therapy for liver diseases. However, the source of primary hepatocytes is limited. We describe a novel non-transgenic protocol that facilitates the rapid generation of hepatocyte-like cells from human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), providing a new source of functional hepatocytes. Methods In this study, we used hUC-MSCs and human induced pluripotent cells (iPSCs) derived mesenchymal stem cells (iMSCs) to investigate the new induction strategy. Passage 3 MSCs were induced into hepatocyte-like cells using small-molecule compounds combined with cell factors in vitro. Functional hit 1 (FH1), a promising small molecule compound was achieved to replace HGF in the hepatocyte maturation stage to induce the hepatocyte-like cells differentiation. Results We rapidly induced hUC-MSCs and human iMSCs into hepatocyte-like cells within 10 days in vitro, and the cells were morphologically similarly to both hepatocytes derived from the hepatocyte growth factor (HGF)-based method and the primary hepatocytes. They expressed mature hepatocyte special genes and achieved functions such as glycogen storage, albumin expression, urea secretion, cytochrome P450 activity, Low-density lipoprotein (LDL) uptake, and indocyanine green (ICG) uptake. Conclusions We successfully established a small-molecule protocol without using HGF to differentiate MSCs into hepatocyte-like cells, which provides a rapid and cost-effective platform for in vitro studies of liver disease.
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Affiliation(s)
- Sang Luo
- State Key Laboratory of Virology, School of Life Sciences, Wuhan University, Wuhan, China
| | - Yang Ai
- State Key Laboratory of Virology, School of Life Sciences, Wuhan University, Wuhan, China
| | - Shuai Xiao
- State Key Laboratory of Virology, School of Life Sciences, Wuhan University, Wuhan, China
| | - Ben Wang
- State Key Laboratory of Virology, School of Life Sciences, Wuhan University, Wuhan, China
| | - Yefu Wang
- State Key Laboratory of Virology, School of Life Sciences, Wuhan University, Wuhan, China
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Al Demour S, Adwan S, Jafar H, Rahmeh R, Alhawari H, Awidi A. Safety and Efficacy of 2 Intracavernous Injections of Allogeneic Wharton's Jelly-Derived Mesenchymal Stem Cells in Diabetic Patients with Erectile Dysfunction: Phase 1/2 Clinical Trial. Urol Int 2021; 105:935-943. [PMID: 34384079 DOI: 10.1159/000517364] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 04/30/2021] [Indexed: 11/19/2022]
Abstract
BACKGROUND AND OBJECTIVES Stem cell therapy is a novel treatment with regenerative ability that can treat erectile dysfunction (ED). This phase 1/2 clinical trial (NCT02945449) using 2 consecutive intracavernous (IC) injections of allogeneic Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) was studied for the first time in the treatment of diabetic patients with ED. The primary outcome was to assess the safety and tolerability, and the secondary outcome was to assess the efficacy of 2 consecutive IC injections of allogeneic WJ-MSCs in diabetic ED. PATIENTS AND METHODS Twenty-two diabetic patients with refractory ED were included. Two consecutive IC injections of allogeneic WJ-MSCs were performed. Tolerability was assessed immediately, and at 24 h, safety was evaluated for 12 months. Efficacy was assessed using International Index of Erectile Function-5 (IIEF-5), Erection Hardness Score (EHS), and Color Duplex Doppler Ultrasound for 12 months. RESULTS The procedure was well-tolerated. Minimal and transient adverse events were redness and bruising at the site of injections. There were no patient-reported serious adverse effects. There were significant improvements in IIEF-5, EHS, peak systolic velocity (PSV) basal, and 20-min PSV, all over the follow-up time points in comparison to the baseline. CONCLUSION This is the first human study with proven tolerability, safety, and efficacy of IC injections of allogeneic WJ-MSCs for the treatment of diabetic patients with ED.
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Affiliation(s)
- Saddam Al Demour
- Division of Urology, Department of Special Surgery, School of Medicine, The University of Jordan, Amman, Jordan
| | - Sofia Adwan
- Cell Therapy Center, The University of Jordan, Amman, Jordan.,Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman, Jordan
| | - Hanan Jafar
- Cell Therapy Center, The University of Jordan, Amman, Jordan.,Department of Anatomy and Histology, School of Medicine, The University of Jordan, Amman, Jordan
| | - Reem Rahmeh
- Cell Therapy Center, The University of Jordan, Amman, Jordan
| | - Hussam Alhawari
- Department of Medicine, School of Medicine, The University of Jordan, Amman, Jordan
| | - Abdalla Awidi
- Cell Therapy Center, The University of Jordan, Amman, Jordan.,Department of Medicine, School of Medicine, The University of Jordan, Amman, Jordan
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RATHORE NS, KASHYAP SK, DEORA ANUPAMA, KUMAR PANKAJ, SINGH J, TALLURI TR. Expression of reprogramming factors in mesenchymal stem cells isolated from equine umbilical cord Wharton’s jelly and amniotic fluid. THE INDIAN JOURNAL OF ANIMAL SCIENCES 2021. [DOI: 10.56093/ijans.v91i2.113818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Stem cells represent the most promising population for regenerative cell therapy and have gained much attention during the recent past. Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into trilineages. Like haematopoietic cells, mesenchymal cells have been shown to proliferate and form fibroblast-like colonies in vitro. Despite major progress in our general knowledge related to the application of adult stem cells, finding alternative sources for bone marrow MSCs has remained a challenge. A wide diversity of isolation procedures for mesenchymal stromal cells from various tissues of the placenta, umbilical cord and Wharton's jelly have been described for humans and other species. In this study, we isolated established umbilical cord Wharton’s jelly as a primary source for isolation of mesenchymal stem cells since it is a rich source of stem cells and no ethical concerns are involved. Equine umbilical cord Wharton’s jelly segments were collected during foaling time and digested enzymatically and cultured in-vitro in culture medium. In addition to the study of their morphology and colony forming units, the expression of reprogramming factors by the isolated MSCs were also studied. The isolated MSCs were observed to be plastic adherent, clonogenic and their morphology were polygonal, star shaped and fibroblast like. They revealed a strong expression of pluripotent stemness markers OCT-4, SOX-2, Nanog and KLF-4. From the current study, it can be concluded that Wharton's jelly is a rich source of stem cells with stemness properties expressing the reprogramming factors and mesenchymal like morphology and could be used as an alternate for the bone marrow derived mesenchymal stem cells for cell based regenerative therapies.
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Shareghi-Oskoue O, Aghebati-Maleki L, Yousefi M. Transplantation of human umbilical cord mesenchymal stem cells to treat premature ovarian failure. Stem Cell Res Ther 2021; 12:454. [PMID: 34380572 PMCID: PMC8359553 DOI: 10.1186/s13287-021-02529-w] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Accepted: 06/02/2021] [Indexed: 12/14/2022] Open
Abstract
As one of the problems and diseases for women before 40 years, premature ovarian failure (POF) could be characterized by amenorrhea, low estrogen levels, infertility, high gonadotropin levels, and lack of mature follicles. Causes of the disease involve some genetic disorders, autoimmunity diseases, and environmental factors. Various approaches have been employed to treat POF, however with limited success. Today, stem cells are used to treat POF, since they have the potential to self-repair and regenerate, and are effective in treating ovarian failure and infertility. As mesenchymal stem cell (MSC) could simultaneously activate several mechanisms, many researchers consider MSC transplantation to be the best and most effective approach in cell therapy. A good source for mesenchymal stem cells is human umbilical cord (HUCMSC). Animal models with cyclophosphamide are required for stem cell treatment and performance of HUCMSC transplantation. Stem cell therapy could indicate the levels of ovarian markers and follicle-stimulating hormone receptor. It also increases ovarian weight, plasma E2 levels, and the amount of standard follicles. Herein, the causes of POF, effective treatment strategies, and the effect of HUCMSC transplantation for the treatment of premature ovarian failure are reviewed. Many studies have been conducted in this field, and the results have shown that stem cell treatment is an effective approach to treat infertility.
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Affiliation(s)
- Oldouz Shareghi-Oskoue
- Stem Cell Research Center, Tabriz University of Medical Science, Tabriz, Iran
- Student's Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Leili Aghebati-Maleki
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Immunology, School of Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Mehdi Yousefi
- Stem Cell Research Center, Tabriz University of Medical Science, Tabriz, Iran.
- Department of Immunology, School of Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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Li Y, Shi G, Han Y, Shang H, Li H, Liang W, Zhao W, Bai L, Qin C. Therapeutic potential of human umbilical cord mesenchymal stem cells on aortic atherosclerotic plaque in a high-fat diet rabbit model. Stem Cell Res Ther 2021; 12:407. [PMID: 34266502 PMCID: PMC8281645 DOI: 10.1186/s13287-021-02490-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Accepted: 07/04/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Atherosclerosis (AS) is a complex disease caused in part by dyslipidemia and chronic inflammation. AS is associated with serious cardiovascular disease and remains the leading cause of mortality worldwide. Mesenchymal stem cells (MSCs) have evolved as an attractive therapeutic agent in various diseases including AS. Human umbilical cord MSCs (UCSCs) have been used in cell therapy trials due to their ability to differentiate and proliferate. The present study aimed to investigate the effect of UCSCs treatment on atherosclerotic plaque formation and the progression of lesions in a high-fat diet rabbit model. METHODS Rabbits were fed a high-fat diet and then randomly divided into three groups: control, model, and treatment groups. Rabbits in the treatment group were injected with UCSCs (6 × 106 in 500 μL phosphate buffered saline) after 1 month of high-fat diet, once every 2 weeks, for 3 months. The model group was given PBS only. We analyzed serum biomarkers, used ultrasound and histopathology to detect arterial plaques and laser Doppler imaging to measure peripheral blood vessel blood filling, and analyzed the intestinal flora and metabolism. RESULTS Histological analysis showed that the aortic plaque area was significantly reduced in the treatment group. We also found a significant decrease in macrophage accumulation and apoptosis, an increase in expression of scavenger receptors CD36 and SRA1, a decrease in uptake of modified low-density protein (ox-LDL), and a decrease in levels of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α following UCSCs treatment. We also found that anti-inflammatory cytokines IL-10 and transforming growth factor (TGF)-β expression increased in the aorta atherosclerotic plaque of the treatment group. UCSCs treatment improved the early peripheral blood filling, reduced the serum lipid level, and inhibited inflammation progression by regulating the intestinal flora dysbiosis caused by the high-fat diet. More specifically, levels of the microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) were down-regulated in the treatment group. CONCLUSIONS UCSCs treatment alleviated atherosclerotic plaque burden by reducing inflammation, regulating the intestinal flora and TMAO levels, and repairing the damaged endothelium.
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Affiliation(s)
- Yanhong Li
- Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health; Institute of Medical Laboratory Animal Science, CAMS&PUMC; Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Beijing, 100021, China
| | - Guiying Shi
- Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health; Institute of Medical Laboratory Animal Science, CAMS&PUMC; Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Beijing, 100021, China
| | - Yunlin Han
- Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health; Institute of Medical Laboratory Animal Science, CAMS&PUMC; Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Beijing, 100021, China
| | - Haiquan Shang
- Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health; Institute of Medical Laboratory Animal Science, CAMS&PUMC; Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Beijing, 100021, China
| | - Huiwu Li
- Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health; Institute of Medical Laboratory Animal Science, CAMS&PUMC; Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Beijing, 100021, China
| | - Wei Liang
- Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health; Institute of Medical Laboratory Animal Science, CAMS&PUMC; Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Beijing, 100021, China
| | - Wenjie Zhao
- Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health; Institute of Medical Laboratory Animal Science, CAMS&PUMC; Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Beijing, 100021, China
| | - Lin Bai
- Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health; Institute of Medical Laboratory Animal Science, CAMS&PUMC; Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Beijing, 100021, China
| | - Chuan Qin
- Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health; Institute of Medical Laboratory Animal Science, CAMS&PUMC; Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Beijing, 100021, China.
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Zhang C. The Roles of Different Stem Cells in Premature Ovarian Failure. Curr Stem Cell Res Ther 2021; 15:473-481. [PMID: 30868961 DOI: 10.2174/1574888x14666190314123006] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Revised: 11/06/2018] [Accepted: 11/08/2018] [Indexed: 02/07/2023]
Abstract
Premature ovarian failure (POF) is characterized by amenorrhea, hypergonadotropism and hypoestrogenism before the age of 40, which affects 1% of women in the general population. POF is complex and heterogeneous due to its pathogenetic mechanisms. It is one of the significant causes of female infertility. Although many treatments are available for POF, these therapies are less efficient and trigger many side effects. Therefore, to find effective therapeutics for POF is urgently required. Due to stem cells having self-renewal and regeneration potential, they may be effective for the treatment of ovarian failure and consequently infertility. Recent studies have found that stem cells therapy may be able to restore the ovarian structure and function in animal models of POF and provide an effective treatment method. The present review summarizes the biological roles and the possible signaling mechanisms of the different stem cells in POF ovary. Further study on the precise mechanisms of stem cells on POF may provide novel insights into the female reproduction, which not only enhances the understanding of the physiological roles but also supports effective therapy for recovering ovarian functions against infertility.
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Affiliation(s)
- Cheng Zhang
- College of Life Science, Capital Normal University, Beijing 100048, China
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Rahmani-Moghadam E, Zarrin V, Mahmoodzadeh A, Owrang M, Talaei-Khozani T. Comparison of the Characteristics of Breast Milk-derived Stem Cells with the Stem Cells Derived from the Other Sources: A Comparative Review. Curr Stem Cell Res Ther 2021; 17:71-90. [PMID: 34161214 DOI: 10.2174/1574888x16666210622125309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 03/14/2021] [Accepted: 03/28/2021] [Indexed: 11/22/2022]
Abstract
Breast milk (BrM) not only supplies nutrition, but it also contains a diverse population of cells. It has been estimated that up to 6% of the cells in human milk possess the characteristics of mesenchymal stem cells (MSC). Available data also indicate that these cells are multipotent and capable of self-renewal and differentiation with other cells. In this review, we have compared different characteristics, such as CD markers, differentiation capacity, and morphology of stem cells, derived from human breast milk (hBr-MSC) with human bone marrow (hBMSC), Wharton's jelly (WJMSC), and human adipose tissue (hADMSC). Through the literature review, it was revealed that human breast milk-derived stem cells specifically express a group of cell surface markers, including CD14, CD31, CD45, and CD86. Importantly, a group of markers, CD13, CD29, CD44, CD105, CD106, CD146, and CD166, were identified, which were common in the four sources of stem cells. WJMSC, hBMSC, hADMSC, and hBr-MSC are potently able to differentiate into the mesoderm, ectoderm, and endoderm cell lineages. The ability of hBr-MSCs todifferentiate into the neural stem cells, neurons, adipocyte, hepatocyte, chondrocyte, osteocyte, and cardiomyocytes has made these cells a promising source of stem cells in regenerative medicine, while isolation of stem cells from the commonly used sources, such as bone marrow, requires invasive procedures. Although autologous breast milk-derived stem cells are an accessible source for women who are in the lactation period, breast milk can be considered as a source of stem cells with high differentiation potential without any ethical concern.
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Affiliation(s)
- Ebrahim Rahmani-Moghadam
- Department of Anatomical sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Vahideh Zarrin
- Laboratory for Stem Cell Research, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amir Mahmoodzadeh
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Marzieh Owrang
- Department of Anatomical sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Tahereh Talaei-Khozani
- Department of Anatomical sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
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Human Mesenchymal Stem Cell Therapy and Other Novel Treatment Approaches for Premature Ovarian Insufficiency. Reprod Sci 2021; 28:1688-1696. [PMID: 33956339 PMCID: PMC8144118 DOI: 10.1007/s43032-021-00528-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 03/01/2021] [Indexed: 12/11/2022]
Abstract
Premature ovarian insufficiency (POI) is a condition characterized by amenorrhea, hypergonadotropic hypogonadism, estrogen deficiency, and reduced follicle counts leading to infertility under the age of 40. POI occurs in approximately 1-3% of women in the general population. Evaluation is warranted when the diagnosis of POI is made to rule out underlying etiologies, which could be multifactorial. This review serves to cover the novel treatment approaches reported in the literature.
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Ülger M, Sezer G, Özyazgan İ, Özocak H, Yay A, Balcıoğlu E, Yalçın B, Göç R, Ülger B, Özyazgan TM, Yakan B. The effect of erythropoietin and umbilical cord-derived mesenchymal stem cells on nerve regeneration in rats with sciatic nerve injury. J Chem Neuroanat 2021; 114:101958. [PMID: 33864937 DOI: 10.1016/j.jchemneu.2021.101958] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 04/05/2021] [Accepted: 04/06/2021] [Indexed: 02/06/2023]
Abstract
OBJECTIVE We aimed to investigate the effects of umbilical cord-derived mesenchymal stem cells and erythropoietin on nerve regeneration in the sciatic nerve 'crush injury' in a rat model. METHODS Experimental animals were randomly divided into 5 groups: Crush Injury, Sham, Crush Injury + Erythropoietin, Crush Injury + Mesenchymal Stem Cell, Crush Injury + Erythropoietin + Mesenchymal Stem Cell groups. Crush injury made with bulldog clamp. Mesencyhmal stem cells delivered by enjection locally. Erythropoietin administered by intraperitoneally. On the 0th, 14th and 28th days, all groups underwent a sciatic functional index test. On 28th day, sciatic nerves were harvested and histopathological appearance, axon number and axon diameter of the sciatic nerves were evaluated with Oil Red O staining. Immunoreactivity of nerve growth factor, neurofilament-H and caspase-3 were determined by immunofluorescence staining in nerve tissue. RESULTS In histopathological examination, axons and nerve bundles exhibiting normal nerve architecture in the Sham group. Crush Injury + Mesenchymal Stem Cell group has similar histological appearance to the Sham group. The number of axons were higher in the Mesenchymal Stem Cell groups compared to the Crush Injury group. Nerve growth factor immunoreactivity intensity was significantly lower in Crush Injury + Mesenchymal Stem Cell group compared to Crush Injury group. Neurofilament-H density was higher in the treatment groups when compared to the Crush Injury group. CONCLUSIONS In this study, it was found that umbilical cord-derived mesenchymal stem cells and erythropoietin treatments effects positively regeneration of crush injury caused by bulldog clamp in the sciatic nerve of rats.
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Affiliation(s)
- Menekşe Ülger
- Department of Histology and Embryology, Erciyes University, Faculty of Medicine, 38039, Kayseri, Turkey.
| | - Gülay Sezer
- Department of Pharmacology, Erciyes University, Faculty of Medicine, 38039, Kayseri, Turkey.
| | - İrfan Özyazgan
- Department of Plastic Reconstructive and Aesthetic Surgery, Erciyes University, Faculty of Medicine, 38039, Kayseri, Turkey.
| | - Hakan Özocak
- Department of Plastic Reconstructive and Aesthetic Surgery, Erciyes University, Faculty of Medicine, 38039, Kayseri, Turkey.
| | - Arzu Yay
- Department of Histology and Embryology, Erciyes University, Faculty of Medicine, 38039, Kayseri, Turkey.
| | - Esra Balcıoğlu
- Department of Histology and Embryology, Erciyes University, Faculty of Medicine, 38039, Kayseri, Turkey.
| | - Betül Yalçın
- Department of Histology and Embryology, Erciyes University, Faculty of Medicine, 38039, Kayseri, Turkey.
| | - Rümeysa Göç
- Department of Histology and Embryology, Cumhuriyet University, Faculty of Medicine, 058140, Sivas, Turkey.
| | - Birkan Ülger
- Department of Anesthesiology and Reanimation, Erciyes University, Faculty of Medicine, 38039, Kayseri, Turkey.
| | - Tuğçe Merve Özyazgan
- Department of Histology and Embryology, Erciyes University, Faculty of Medicine, 38039, Kayseri, Turkey.
| | - Birkan Yakan
- Department of Histology and Embryology, Erciyes University, Faculty of Medicine, 38039, Kayseri, Turkey.
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Chae DS, Han JH, Park YJ, Kim SW. TGF-β1 overexpressing human MSCs generated using gene editing show robust therapeutic potential for treating collagen-induced arthritis. J Tissue Eng Regen Med 2021; 15:513-523. [PMID: 33749143 DOI: 10.1002/term.3191] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 11/29/2020] [Accepted: 03/12/2021] [Indexed: 12/14/2022]
Abstract
Transforming growth factor β (TGF-β) plays a pivotal role in cartilage differentiation and other functions of mesenchymal stem cells (MSCs). In this study, we investigated the therapeutic potential of TGF-β1 overexpressing amniotic MSCs (AMMs) generated using gene editing in a mouse model of damaged cartilage. The TGF-β1 gene was inserted into a safe harbor genomic locus in AMMs using transcription activator-like effector nucleases. The chondrogenic properties of TGF-β1-overexpressing AMMs (AMM/T) were characterized using reverse transcription polymerase chain reaction (RT-PCR), quantitative RT-PCR, and histological analysis, and their therapeutic effects were evaluated in mouse model of collagen-induced arthritis (CIA). AMM/T expressed cartilage-specific genes and showed intense Safranin O and Alcian blue staining. Furthermore, injecting AMM/T attenuated CIA progression compared with AMM injection, and increased the regulatory T (Treg) cell population, while suppressing T helper (Th)17 cell activation in CIA mice. Proinflammatory factors, such as interleukin-1β (IL-1β), IL-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α were significantly decreased in AMM/T injected CIA mice compared with their AMM injected counterparts. In conclusion, genome-edited AMMs overexpressing TGF-β1 may be a novel and alternative therapeutic option for protecting cartilage and treating inflammatory joint arthritis.
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Affiliation(s)
- Dong-Sik Chae
- Department of Orthopedic Surgery, Catholic Kwandong University College of Medicine, International St. Mary's Hospital, Incheon, Republic of Korea
| | - Ju Hye Han
- Department Medicine, Catholic Kwandong University College of Medicine, Gangneung, Republic of Korea
| | - Young-Jin Park
- Department of Family Medicine, Dong-A University College of Medicine, Dong-A University Medical Center, Busan, Republic of Korea
| | - Sung-Whan Kim
- Department Medicine, Catholic Kwandong University College of Medicine, Gangneung, Republic of 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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Altundag Ö, Çelebi-Saltik B. From Embryo to Adult: One Carbon Metabolism in Stem Cells. Curr Stem Cell Res Ther 2021; 16:175-188. [PMID: 32652922 DOI: 10.2174/1574888x15666200712191308] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 04/16/2020] [Accepted: 04/23/2020] [Indexed: 11/22/2022]
Abstract
Stem cells are undifferentiated cells with self-renewal property and varying differentiation potential that allow the regeneration of tissue cells of an organism throughout adult life beginning from embryonic development. Through the asymmetric cell divisions, each stem cell replicates itself and produces an offspring identical with the mother cell, and a daughter cell that possesses the characteristics of a progenitor cell and commits to a specific lineage to differentiate into tissue cells to maintain homeostasis. To maintain a pool of stem cells to ensure tissue regeneration and homeostasis, it is important to regulate the metabolic functioning of stem cells, progenitor cells and adult tissue stem cells that will meet their internal and external needs. Upon fertilization, the zygote transforms metabolic reprogramming while implantation, embryonic development, organogenesis processes and after birth through adult life. Metabolism in stem cells is a concept that is relatively new to be enlightened. There are no adequate and comprehensive in vitro studies on the comparative analysis of the effects of one-carbon (1-C) metabolism on fetal and adult stem cells compared to embryonic and cancer stem cells' studies that have been reported recently. Since 1-C metabolism is linking parental environmental/ dietary factors and fetal development, investigating the epigenetic, genetic, metabolic and developmental effects on adult period is necessary. Several mutations and abnormalities in 1-C metabolism have been noted in disease changing from diabetes, cancer, pregnancy-related outcomes such as pre-eclampsia, spontaneous abortion, placental abruption, premature delivery, and cardiovascular diseases. In this review, the effects of 1-C metabolism, mainly the methionine and folate metabolism, in stem cells that exist in different developmental stages will be discussed.
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Affiliation(s)
- Özlem Altundag
- Department of Stem Cell Sciences, Hacettepe University Graduate School of Health Sciences, 06100, Sihhiye, Ankara, Turkey
| | - Betül Çelebi-Saltik
- Department of Stem Cell Sciences, Hacettepe University Graduate School of Health Sciences, 06100, Sihhiye, Ankara, Turkey
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Li KD, Wang Y, Sun Q, Li MS, Chen JL, Liu L. Rabbit umbilical cord mesenchymal stem cells: A new option for tissue engineering. J Gene Med 2021; 23:e3282. [PMID: 33047422 DOI: 10.1002/jgm.3282] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 09/17/2020] [Accepted: 09/30/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The source and availability of cells for tissue engineering in large scale research or clinical trials requires special attention. We propose the idea of applying rabbit umbilical cord mesenchymal stem cells for this purpose. METHODS Here, the structure of the rabbit umbilical cord was analyzed and compared to that of human umbilical cord, both macroscopically and histologically. Next, we isolated, cultured and identified the proliferative activity and immunological characteristics of rabbit umbilical cord mesenchymal stem cells in vitro using mixed lymphocyte reaction, flow cytometry and an enzyme-linked immunosorbent assay. Furthermore, we evaluated the effects of biphasic calcium phosphate ceramic scaffolds seeded with rabbit umbilical cord mesenchymal stem cells in rat cranial defect models using multiple techniques, including radiological, histological and immunohistochemistry. RESULTS In vitro studies demonstated a high level of proliferation and multi-lineage differentiation potential in rabbit umbilical cord mesenchymal stem cells. Rabbit umbilical cord mesenchymal stem cells exibited low immunogenicity properties and immune suppression capability with respect to both the allogeneic and xenogeneic immune response. The results of the in vivo study showed that rabbit umbilical cord mesenchymal stem cells could promote osteogenesis in heterogeneous hosts. CONCLUSIONS The rabbit umbilical cord mesenchymal stem cells may be a new source for tissue engineering.
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Affiliation(s)
- Kai-De Li
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, China
| | - Yi Wang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, China
- Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China
| | - Quan Sun
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, China
| | - Mei-Sheng Li
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, China
| | - Jin-Long Chen
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, China
| | - Lei Liu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, China
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de la Torre P, Flores AI. Current Status and Future Prospects of Perinatal Stem Cells. Genes (Basel) 2020; 12:genes12010006. [PMID: 33374593 PMCID: PMC7822425 DOI: 10.3390/genes12010006] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [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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Silini AR, Di Pietro R, Lang-Olip I, Alviano F, Banerjee A, Basile M, Borutinskaite V, Eissner G, Gellhaus A, Giebel B, Huang YC, Janev A, Kreft ME, Kupper N, Abadía-Molina AC, Olivares EG, Pandolfi A, Papait A, Pozzobon M, Ruiz-Ruiz C, Soritau O, Susman S, Szukiewicz D, Weidinger A, Wolbank S, Huppertz B, Parolini O. Perinatal Derivatives: Where Do We Stand? A Roadmap of the Human Placenta and Consensus for Tissue and Cell Nomenclature. Front Bioeng Biotechnol 2020; 8:610544. [PMID: 33392174 PMCID: PMC7773933 DOI: 10.3389/fbioe.2020.610544] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Accepted: 11/23/2020] [Indexed: 02/05/2023] Open
Abstract
Progress in the understanding of the biology of perinatal tissues has contributed to the breakthrough revelation of the therapeutic effects of perinatal derivatives (PnD), namely birth-associated tissues, cells, and secreted factors. The significant knowledge acquired in the past two decades, along with the increasing interest in perinatal derivatives, fuels an urgent need for the precise identification of PnD and the establishment of updated consensus criteria policies for their characterization. The aim of this review is not to go into detail on preclinical or clinical trials, but rather we address specific issues that are relevant for the definition/characterization of perinatal cells, starting from an understanding of the development of the human placenta, its structure, and the different cell populations that can be isolated from the different perinatal tissues. We describe where the cells are located within the placenta and their cell morphology and phenotype. We also propose nomenclature for the cell populations and derivatives discussed herein. This review is a joint effort from the COST SPRINT Action (CA17116), which broadly aims at approaching consensus for different aspects of PnD research, such as providing inputs for future standards for the processing and in vitro characterization and clinical application of PnD.
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Affiliation(s)
- Antonietta Rosa Silini
- Centro di Ricerca E. Menni, Fondazione Poliambulanza-Istituto Ospedaliero, Brescia, Italy
| | - Roberta Di Pietro
- Department of Medicine and Ageing Sciences, G. d’Annunzio University of Chieti-Pescara, Chieti, Italy
- StemTeCh Group, G. d’Annunzio Foundation, G. d’Annunzio University of Chieti-Pescara, Chieti, Italy
| | - Ingrid Lang-Olip
- Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria
| | - Francesco Alviano
- Department of Experimental, Diagnostic and Specialty Medicine, Unit of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy
| | - Asmita Banerjee
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Austrian Cluster for Tissue Regeneration, Vienna, Austria
| | - Mariangela Basile
- Department of Medicine and Ageing Sciences, G. d’Annunzio University of Chieti-Pescara, Chieti, Italy
- StemTeCh Group, G. d’Annunzio Foundation, G. d’Annunzio University of Chieti-Pescara, Chieti, Italy
| | - Veronika Borutinskaite
- Department of Molecular Cell Biology, Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania
| | - Günther Eissner
- Systems Biology Ireland, School of Medicine, University College Dublin, Dublin, Ireland
| | - Alexandra Gellhaus
- Department of Gynecology and Obstetrics, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Bernd Giebel
- Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Yong-Can Huang
- Shenzhen Engineering Laboratory of Orthopaedic Regenerative Technologies, Department of Spine Surgery, Peking University Shenzhen Hospital, Shenzhen, China
| | - Aleksandar Janev
- Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Mateja Erdani Kreft
- Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Nadja Kupper
- Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria
| | - Ana Clara Abadía-Molina
- Instituto de Biopatología y Medicina Regenerativa, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain
- Departamento de Bioquímica y Biología Molecular III e Inmunología, Universidad de Granada, Granada, Spain
| | - Enrique G. Olivares
- Instituto de Biopatología y Medicina Regenerativa, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain
- Departamento de Bioquímica y Biología Molecular III e Inmunología, Universidad de Granada, Granada, Spain
- Unidad de Gestión Clínica Laboratorios, Hospital Universitario Clínico San Cecilio, Granada, Spain
| | - Assunta Pandolfi
- StemTeCh Group, G. d’Annunzio Foundation, G. d’Annunzio University of Chieti-Pescara, Chieti, Italy
- Vascular and Stem Cell Biology, Department of Medical, Oral and Biotechnological Sciences, G. d’Annunzio University of Chieti-Pescara, CAST (Center for Advanced Studies and Technology, ex CeSI-MeT), Chieti, Italy
| | - Andrea Papait
- Centro di Ricerca E. Menni, Fondazione Poliambulanza-Istituto Ospedaliero, Brescia, Italy
- Department of Life Science and Public Health, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Michela Pozzobon
- Stem Cells and Regenerative Medicine Lab, Department of Women’s and Children’s Health, University of Padova, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padua, Italy
| | - Carmen Ruiz-Ruiz
- Instituto de Biopatología y Medicina Regenerativa, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain
- Departamento de Bioquímica y Biología Molecular III e Inmunología, Universidad de Granada, Granada, Spain
| | - Olga Soritau
- The Oncology Institute “Prof. Dr. Ion Chiricuta”, Cluj-Napoca, Romania
| | - Sergiu Susman
- Department of Morphological Sciences-Histology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Department of Pathology, IMOGEN Research Center, Cluj-Napoca, Romania
| | - Dariusz Szukiewicz
- Department of General and Experimental Pathology with Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, Warsaw, Poland
| | - Adelheid Weidinger
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Austrian Cluster for Tissue Regeneration, Vienna, Austria
| | - Susanne Wolbank
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Austrian Cluster for Tissue Regeneration, Vienna, Austria
| | - Berthold Huppertz
- Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria
| | - Ornella Parolini
- Department of Life Science and Public Health, Università Cattolica del Sacro Cuore, Rome, Italy
- Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, Italy
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Ramdan M, Bigdeli MR, Khaksar S, Aliaghaei A. Evaluating the effect of transplanting umbilical cord matrix stem cells on ischemic tolerance in an animal model of stroke. Neurol Res 2020; 43:225-238. [PMID: 33167823 DOI: 10.1080/01616412.2020.1839698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
OBJECTIVE Stroke, a cerebrovascular disease, has been introduced as the second cause of death and physical disability in the world. Recently, cell-based therapy has been considered by the scientific community as a promising strategy for reducing ischemic damages. The stem cells of the umbilical cord release growth and neurotrophic factors. The remarkable properties of these cells are the reason why they were selected as a potential candidate in the present research. METHODS In this study, the impact of transplanting umbilical cord stem cells on injuries resulting from ischemia was investigated. The male rats were categorized into three major. Using stereotaxic surgery, stem cells were injected to the right striatum of the brain. One week after transplantation, cerebral ischemic induction surgery was performed. The rats in the transplantation + ischemia group were separately divided into distinct sub-groups to explore the score of the neurological deficits, infarction volume, integrity of the blood-brain barrier, and brain edema. RESULTS In this study, a significant decrease was observed in the neurological deficits of the transplantation + ischemia group compared with those of the control group. Similarly, the volume of infarction, the permeability of the blood-brain barrier, and edema were significantly reduced in the transplantation + ischemia group in comparison with those of the control group. CONCLUSION The pretreatment of the transplanted umbilical cord stem cells in the striatum of ischemic rats possibly leads to restorative events, exerting a decreasing effect on cell death. Subsequently, these events may improve the motor ability and reduce ischemic injuries.
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Affiliation(s)
- Mahmoud Ramdan
- Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University , Tehran, Iran
| | - Mohammad Reza Bigdeli
- Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University , Tehran, Iran.,Inistitute for Cognitive and Brain Science, Shahid Beheshti University , Tehran, Iran
| | - Sepideh Khaksar
- Department of Plant Sciences, Biological Sciences, Alzahra University , Tehran, Iran
| | - Abbas Aliaghaei
- Anatomy Department, Shahid Beheshti University of Medical Sciences , Tehran, Iran
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