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Rejuvenated ageing mesenchymal stem cells by stepwise preconditioning ameliorates surgery-induced osteoarthritis in rabbits
AIMS: Ageing-related incompetence becomes a major hurdle for the clinical translation of adult stem cells in the treatment of osteoarthritis (OA). This study aims to investigate the effect of stepwise preconditioning on cellular behaviours in human mesenchymal stem cells (hMSCs) from ageing patients...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The British Editorial Society of Bone & Joint Surgery
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845463/ https://www.ncbi.nlm.nih.gov/pubmed/33382341 http://dx.doi.org/10.1302/2046-3758.101.BJR-2020-0249.R1 |
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author | Zong, Zhixian Zhang, Xiaoting Yang, Zhengmeng Yuan, Weihao Huang, Jianping Lin, Weiping Chen, Ting Yu, Jiahao Chen, Jiming Cui, Liao Li, Gang Wei, Bo Lin, Sien |
author_facet | Zong, Zhixian Zhang, Xiaoting Yang, Zhengmeng Yuan, Weihao Huang, Jianping Lin, Weiping Chen, Ting Yu, Jiahao Chen, Jiming Cui, Liao Li, Gang Wei, Bo Lin, Sien |
author_sort | Zong, Zhixian |
collection | PubMed |
description | AIMS: Ageing-related incompetence becomes a major hurdle for the clinical translation of adult stem cells in the treatment of osteoarthritis (OA). This study aims to investigate the effect of stepwise preconditioning on cellular behaviours in human mesenchymal stem cells (hMSCs) from ageing patients, and to verify their therapeutic effect in an OA animal model. METHODS: Mesenchymal stem cells (MSCs) were isolated from ageing patients and preconditioned with chondrogenic differentiation medium, followed by normal growth medium. Cellular assays including Bromodeoxyuridine / 5-bromo-2'-deoxyuridine (BrdU), quantitative polymerase chain reaction (q-PCR), β-Gal, Rosette forming, and histological staining were compared in the manipulated human mesenchymal stem cells (hM-MSCs) and their controls. The anterior cruciate ligament transection (ACLT) rabbit models were locally injected with two millions, four millions, or eight millions of hM-MSCs or phosphate-buffered saline (PBS). Osteoarthritis Research Society International (OARSI) scoring was performed to measure the pathological changes in the affected joints after staining. Micro-CT analysis was conducted to determine the microstructural changes in subchondral bone. RESULTS: Stepwise preconditioning approach significantly enhanced the proliferation and chondrogenic potential of ageing hMSCs at early passage. Interestingly, remarkably lower immunogenicity and senescence was also found in hM-MSCs. Data from animal studies showed cartilage damage was retarded and subchondral bone remodelling was prevented by the treatment of preconditioned MSCs. The therapeutic effect depended on the number of cells applied to animals, with the best effect observed when treated with eight millions of hM-MSCs. CONCLUSION: This study demonstrated a reliable and feasible stepwise preconditioning strategy to improve the safety and efficacy of ageing MSCs for the prevention of OA development. Cite this article: Bone Joint Res 2021;10(1):10–21. |
format | Online Article Text |
id | pubmed-7845463 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The British Editorial Society of Bone & Joint Surgery |
record_format | MEDLINE/PubMed |
spelling | pubmed-78454632021-02-01 Rejuvenated ageing mesenchymal stem cells by stepwise preconditioning ameliorates surgery-induced osteoarthritis in rabbits Zong, Zhixian Zhang, Xiaoting Yang, Zhengmeng Yuan, Weihao Huang, Jianping Lin, Weiping Chen, Ting Yu, Jiahao Chen, Jiming Cui, Liao Li, Gang Wei, Bo Lin, Sien Bone Joint Res Cartilage AIMS: Ageing-related incompetence becomes a major hurdle for the clinical translation of adult stem cells in the treatment of osteoarthritis (OA). This study aims to investigate the effect of stepwise preconditioning on cellular behaviours in human mesenchymal stem cells (hMSCs) from ageing patients, and to verify their therapeutic effect in an OA animal model. METHODS: Mesenchymal stem cells (MSCs) were isolated from ageing patients and preconditioned with chondrogenic differentiation medium, followed by normal growth medium. Cellular assays including Bromodeoxyuridine / 5-bromo-2'-deoxyuridine (BrdU), quantitative polymerase chain reaction (q-PCR), β-Gal, Rosette forming, and histological staining were compared in the manipulated human mesenchymal stem cells (hM-MSCs) and their controls. The anterior cruciate ligament transection (ACLT) rabbit models were locally injected with two millions, four millions, or eight millions of hM-MSCs or phosphate-buffered saline (PBS). Osteoarthritis Research Society International (OARSI) scoring was performed to measure the pathological changes in the affected joints after staining. Micro-CT analysis was conducted to determine the microstructural changes in subchondral bone. RESULTS: Stepwise preconditioning approach significantly enhanced the proliferation and chondrogenic potential of ageing hMSCs at early passage. Interestingly, remarkably lower immunogenicity and senescence was also found in hM-MSCs. Data from animal studies showed cartilage damage was retarded and subchondral bone remodelling was prevented by the treatment of preconditioned MSCs. The therapeutic effect depended on the number of cells applied to animals, with the best effect observed when treated with eight millions of hM-MSCs. CONCLUSION: This study demonstrated a reliable and feasible stepwise preconditioning strategy to improve the safety and efficacy of ageing MSCs for the prevention of OA development. Cite this article: Bone Joint Res 2021;10(1):10–21. The British Editorial Society of Bone & Joint Surgery 2020-12-31 /pmc/articles/PMC7845463/ /pubmed/33382341 http://dx.doi.org/10.1302/2046-3758.101.BJR-2020-0249.R1 Text en © 2021 Author(s) et al. https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND 4.0) licence, which permits the copying and redistribution of the work only, and provided the original author and source are credited. See https://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Cartilage Zong, Zhixian Zhang, Xiaoting Yang, Zhengmeng Yuan, Weihao Huang, Jianping Lin, Weiping Chen, Ting Yu, Jiahao Chen, Jiming Cui, Liao Li, Gang Wei, Bo Lin, Sien Rejuvenated ageing mesenchymal stem cells by stepwise preconditioning ameliorates surgery-induced osteoarthritis in rabbits |
title | Rejuvenated ageing mesenchymal stem cells by stepwise preconditioning ameliorates surgery-induced osteoarthritis in rabbits |
title_full | Rejuvenated ageing mesenchymal stem cells by stepwise preconditioning ameliorates surgery-induced osteoarthritis in rabbits |
title_fullStr | Rejuvenated ageing mesenchymal stem cells by stepwise preconditioning ameliorates surgery-induced osteoarthritis in rabbits |
title_full_unstemmed | Rejuvenated ageing mesenchymal stem cells by stepwise preconditioning ameliorates surgery-induced osteoarthritis in rabbits |
title_short | Rejuvenated ageing mesenchymal stem cells by stepwise preconditioning ameliorates surgery-induced osteoarthritis in rabbits |
title_sort | rejuvenated ageing mesenchymal stem cells by stepwise preconditioning ameliorates surgery-induced osteoarthritis in rabbits |
topic | Cartilage |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845463/ https://www.ncbi.nlm.nih.gov/pubmed/33382341 http://dx.doi.org/10.1302/2046-3758.101.BJR-2020-0249.R1 |
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