Human adipose-derived stromal/stem cells expressing doublecortin improve cartilage repair in rabbits and monkeys

Abstract Localized cartilage lesions in early osteoarthritis and acute joint injuries are usually treated surgically to restore function and relieve pain. However, a persistent clinical challenge remains in how to repair the cartilage lesions. We expressed doublecortin (DCX) in human adipose-derived...

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Autores principales:	Dongxia Ge, Michael J. O’Brien, Felix H. Savoie, Jeffrey M. Gimble, Xiying Wu, Margaret H. Gilbert, Gabrielle L. Clark-Patterson, Jason D. Schuster, Kristin S. Miller, Alun Wang, Leann Myers, Zongbing You
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/817693d80fe147a099eeab83664e6183
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spelling	oai:doaj.org-article:817693d80fe147a099eeab83664e61832021-12-05T12:24:35ZHuman adipose-derived stromal/stem cells expressing doublecortin improve cartilage repair in rabbits and monkeys10.1038/s41536-021-00192-62057-3995https://doaj.org/article/817693d80fe147a099eeab83664e61832021-11-01T00:00:00Zhttps://doi.org/10.1038/s41536-021-00192-6https://doaj.org/toc/2057-3995Abstract Localized cartilage lesions in early osteoarthritis and acute joint injuries are usually treated surgically to restore function and relieve pain. However, a persistent clinical challenge remains in how to repair the cartilage lesions. We expressed doublecortin (DCX) in human adipose-derived stromal/stem cells (hASCs) and engineered hASCs into cartilage tissues using an in vitro 96-well pellet culture system. The cartilage tissue constructs with and without DCX expression were implanted in the knee cartilage defects of rabbits (n = 42) and monkeys (n = 12). Cohorts of animals were euthanized at 6, 12, and 24 months after surgery to evaluate the cartilage repair outcomes. We found that DCX expression in hASCs increased expression of growth differentiation factor 5 (GDF5) and matrilin 2 in the engineered cartilage tissues. The cartilage tissues with DCX expression significantly enhanced cartilage repair as assessed macroscopically and histologically at 6, 12, and 24 months after implantation in the rabbits and 24 months after implantation in the monkeys, compared to the cartilage tissues without DCX expression. These findings suggest that hASCs expressing DCX may be engineered into cartilage tissues that can be used to treat localized cartilage lesions.Dongxia GeMichael J. O’BrienFelix H. SavoieJeffrey M. GimbleXiying WuMargaret H. GilbertGabrielle L. Clark-PattersonJason D. SchusterKristin S. MillerAlun WangLeann MyersZongbing YouNature PortfolioarticleMedicineRENnpj Regenerative Medicine, Vol 6, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Dongxia Ge Michael J. O’Brien Felix H. Savoie Jeffrey M. Gimble Xiying Wu Margaret H. Gilbert Gabrielle L. Clark-Patterson Jason D. Schuster Kristin S. Miller Alun Wang Leann Myers Zongbing You Human adipose-derived stromal/stem cells expressing doublecortin improve cartilage repair in rabbits and monkeys
description	Abstract Localized cartilage lesions in early osteoarthritis and acute joint injuries are usually treated surgically to restore function and relieve pain. However, a persistent clinical challenge remains in how to repair the cartilage lesions. We expressed doublecortin (DCX) in human adipose-derived stromal/stem cells (hASCs) and engineered hASCs into cartilage tissues using an in vitro 96-well pellet culture system. The cartilage tissue constructs with and without DCX expression were implanted in the knee cartilage defects of rabbits (n = 42) and monkeys (n = 12). Cohorts of animals were euthanized at 6, 12, and 24 months after surgery to evaluate the cartilage repair outcomes. We found that DCX expression in hASCs increased expression of growth differentiation factor 5 (GDF5) and matrilin 2 in the engineered cartilage tissues. The cartilage tissues with DCX expression significantly enhanced cartilage repair as assessed macroscopically and histologically at 6, 12, and 24 months after implantation in the rabbits and 24 months after implantation in the monkeys, compared to the cartilage tissues without DCX expression. These findings suggest that hASCs expressing DCX may be engineered into cartilage tissues that can be used to treat localized cartilage lesions.
format	article
author	Dongxia Ge Michael J. O’Brien Felix H. Savoie Jeffrey M. Gimble Xiying Wu Margaret H. Gilbert Gabrielle L. Clark-Patterson Jason D. Schuster Kristin S. Miller Alun Wang Leann Myers Zongbing You
author_facet	Dongxia Ge Michael J. O’Brien Felix H. Savoie Jeffrey M. Gimble Xiying Wu Margaret H. Gilbert Gabrielle L. Clark-Patterson Jason D. Schuster Kristin S. Miller Alun Wang Leann Myers Zongbing You
author_sort	Dongxia Ge
title	Human adipose-derived stromal/stem cells expressing doublecortin improve cartilage repair in rabbits and monkeys
title_short	Human adipose-derived stromal/stem cells expressing doublecortin improve cartilage repair in rabbits and monkeys
title_full	Human adipose-derived stromal/stem cells expressing doublecortin improve cartilage repair in rabbits and monkeys
title_fullStr	Human adipose-derived stromal/stem cells expressing doublecortin improve cartilage repair in rabbits and monkeys
title_full_unstemmed	Human adipose-derived stromal/stem cells expressing doublecortin improve cartilage repair in rabbits and monkeys
title_sort	human adipose-derived stromal/stem cells expressing doublecortin improve cartilage repair in rabbits and monkeys
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/817693d80fe147a099eeab83664e6183
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Human adipose-derived stromal/stem cells expressing doublecortin improve cartilage repair in rabbits and monkeys

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