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Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes

Autologous chondrocyte implantation (ACI) depends on the quality and quantity of implanted cells and is hindered by the fact that chondrocytes cultured for long periods of time undergo dedifferentiation. Here we have developed a reproducible and efficient chondrogenic protocol to redifferentiate cho...

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Autores principales: Jiménez, G., López-Ruiz, E., Kwiatkowski, W., Montañez, E., Arrebola, F., Carrillo, E., Gray, P. C., Belmonte, J. C. Izpisua, Choe, S., Perán, M., Marchal, J. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643338/
https://www.ncbi.nlm.nih.gov/pubmed/26563344
http://dx.doi.org/10.1038/srep16400
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author Jiménez, G.
López-Ruiz, E.
Kwiatkowski, W.
Montañez, E.
Arrebola, F.
Carrillo, E.
Gray, P. C.
Belmonte, J. C. Izpisua
Choe, S.
Perán, M.
Marchal, J. A.
author_facet Jiménez, G.
López-Ruiz, E.
Kwiatkowski, W.
Montañez, E.
Arrebola, F.
Carrillo, E.
Gray, P. C.
Belmonte, J. C. Izpisua
Choe, S.
Perán, M.
Marchal, J. A.
author_sort Jiménez, G.
collection PubMed
description Autologous chondrocyte implantation (ACI) depends on the quality and quantity of implanted cells and is hindered by the fact that chondrocytes cultured for long periods of time undergo dedifferentiation. Here we have developed a reproducible and efficient chondrogenic protocol to redifferentiate chondrocytes isolated from osteoarthritis (OA) patients. We used morphological, histological and immunological analysis together with a RT-PCR detection of collagen I and collagen II gene expression to show that chondrocytes isolated from articular cartilage biopsies of patients and subjected to long-term culture undergo dedifferentiation and that these cells can be redifferentiated following treatment with the chimeric Activin A/BMP2 ligand AB235. Examination of AB235-treated cell pellets in both in vitro and in vivo experiments revealed that redifferentiated chondrocytes synthesized a cartilage-specific extracellular matrix (ECM), primarily consisting of vertically-orientated collagen fibres and cartilage-specific proteoglycans. AB235-treated cell pellets also integrated into the surrounding subcutaneous tissue following transplantation in mice as demonstrated by their dramatic increase in size while non-treated control pellets disintegrated upon transplantation. Thus, our findings describe an effective protocol for the promotion of redifferentiation of autologous chondrocytes obtained from OA patients and the formation of a cartilage-like ECM that can integrate into the surrounding tissue in vivo.
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spelling pubmed-46433382015-11-20 Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes Jiménez, G. López-Ruiz, E. Kwiatkowski, W. Montañez, E. Arrebola, F. Carrillo, E. Gray, P. C. Belmonte, J. C. Izpisua Choe, S. Perán, M. Marchal, J. A. Sci Rep Article Autologous chondrocyte implantation (ACI) depends on the quality and quantity of implanted cells and is hindered by the fact that chondrocytes cultured for long periods of time undergo dedifferentiation. Here we have developed a reproducible and efficient chondrogenic protocol to redifferentiate chondrocytes isolated from osteoarthritis (OA) patients. We used morphological, histological and immunological analysis together with a RT-PCR detection of collagen I and collagen II gene expression to show that chondrocytes isolated from articular cartilage biopsies of patients and subjected to long-term culture undergo dedifferentiation and that these cells can be redifferentiated following treatment with the chimeric Activin A/BMP2 ligand AB235. Examination of AB235-treated cell pellets in both in vitro and in vivo experiments revealed that redifferentiated chondrocytes synthesized a cartilage-specific extracellular matrix (ECM), primarily consisting of vertically-orientated collagen fibres and cartilage-specific proteoglycans. AB235-treated cell pellets also integrated into the surrounding subcutaneous tissue following transplantation in mice as demonstrated by their dramatic increase in size while non-treated control pellets disintegrated upon transplantation. Thus, our findings describe an effective protocol for the promotion of redifferentiation of autologous chondrocytes obtained from OA patients and the formation of a cartilage-like ECM that can integrate into the surrounding tissue in vivo. Nature Publishing Group 2015-11-13 /pmc/articles/PMC4643338/ /pubmed/26563344 http://dx.doi.org/10.1038/srep16400 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Jiménez, G.
López-Ruiz, E.
Kwiatkowski, W.
Montañez, E.
Arrebola, F.
Carrillo, E.
Gray, P. C.
Belmonte, J. C. Izpisua
Choe, S.
Perán, M.
Marchal, J. A.
Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes
title Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes
title_full Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes
title_fullStr Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes
title_full_unstemmed Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes
title_short Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes
title_sort activin a/bmp2 chimera ab235 drives efficient redifferentiation of long term cultured autologous chondrocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643338/
https://www.ncbi.nlm.nih.gov/pubmed/26563344
http://dx.doi.org/10.1038/srep16400
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