RT Journal Article
T1 Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes.
A1 Jiménez, G.
A1 López-Ruiz, E.
A1 Kwiatkowski, W.
A1 Montañez, E.
A1 Arrebola, F.
A1 Carrillo, E.
A1 Gray, P. C.
A1 Izpisua Belmonte, J. C.
A1 Choe, S.
A1 Perán, M.
A1 Marchal, J. A.
K1 Activinas
K1 Animales
K1 Biopsia
K1 Cartílago articular
K1 Condrocitos
K1 Colágeno
K1 Matriz extracelular
K1 Humanos
K1 Osteoartritis
K1 Proteoglicanos
K1 Reacción en cadena de la polimerasa de transcriptasa inversa
K1 Tejido subcutáneo
AB 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.
PB Nature Publishing Group
YR 2015
FD 2015-11-13
LK http://hdl.handle.net/10668/2314
UL http://hdl.handle.net/10668/2314
LA en
NO Jiménez G, López-Ruiz E, Kwiatkowski W, Montañez E, Arrebola F, Carrillo E, et al. Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes. Sci Rep. 2015; 5:16400
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 8, 2025