Failure of in vitro–differentiated mesenchymal stem cells from the synovial membrane to form ectopic stable cartilage in vivo
Article first published online: 9 JAN 2004
Copyright © 2004 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 50, Issue 1, pages 142–150, January 2004
How to Cite
De Bari, C., Dell'Accio, F. and Luyten, F. P. (2004), Failure of in vitro–differentiated mesenchymal stem cells from the synovial membrane to form ectopic stable cartilage in vivo. Arthritis & Rheumatism, 50: 142–150. doi: 10.1002/art.11450
- Issue published online: 9 JAN 2004
- Article first published online: 9 JAN 2004
- Manuscript Accepted: 25 SEP 2003
- Manuscript Received: 30 MAY 2003
- FWO. Grant Number: G.0192.99
- IWT. Grant Number: N.000259
We previously reported the identification in a nude mouse assay of molecular markers predictive of the capacity of articular cartilage–derived cells (ACDCs) to form ectopic stable cartilage that is resistant to vascular invasion and endochondral ossification. In the present study, we investigated whether in vitro–differentiated mesenchymal stem cells (MSCs) from the synovial membrane (SM) express the stable-chondrocyte markers and form ectopic stable cartilage in vivo.
Chondrogenesis was induced in micromass culture with the addition of transforming growth factor β1 (TGFβ1). After acquisition of the cartilage phenotype, micromasses were implanted subcutaneously into nude mice. Alternatively, cells were released enzymatically and either replated in monolayer or injected intramuscularly into nude mice. Marker analysis was performed by quantitative reverse transcription–polymerase chain reaction. Cell death was detected with TUNEL assay.
Cartilage-like micromasses and released cells expressed the stable-chondrocyte markers at levels comparable with those expressed by stable ACDCs. The released cells lost chondrocyte marker expression by 24 hours in monolayer and failed to form cartilage when injected intramuscularly into nude mice. Instead, myogenic differentiation was detected. When intact TGFβ1-treated micromasses were implanted subcutaneously, they partially lost their cartilage phenotype and underwent cell death and neoangiogenesis within 1 week. At later time points (15–40 days), we retrieved neither cartilage nor bone, and human cells were not detectable.
The chondrocyte-like phenotype of human SM MSCs, induced in vitro under specific conditions, appears to be unstable and is not sufficient to obtain ectopic formation of stable cartilage in vivo. Studies in animal models of joint surface defect repair are necessary to evaluate the stability of the SM MSC chondrocyte-like phenotype within the joint environment.