Failure of in vitro–differentiated mesenchymal stem cells from the synovial membrane to form ectopic stable cartilage in vivo
Open Access
- 9 January 2004
- journal article
- research article
- Published by Wiley in Arthritis & Rheumatism
- Vol. 50 (1), 142-150
- https://doi.org/10.1002/art.11450
Abstract
Objective 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. Methods 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. Results 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. Conclusion 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.Keywords
This publication has 26 references indexed in Scilit:
- Expanded phenotypically stable chondrocytes persist in the repair tissue and contribute to cartilage matrix formation and structural integration in a goat model of autologous chondrocyte implantationJournal of Orthopaedic Research, 2003
- Skeletal tissue engineering: opportunities and challengesBest Practice & Research Clinical Rheumatology, 2001
- Two- to 9-Year Outcome After Autologous Chondrocyte Transplantation of the KneeClinical Orthopaedics and Related Research, 2000
- Multilineage Potential of Adult Human Mesenchymal Stem CellsScience, 1999
- Mesenchymal stem cellsJournal of Orthopaedic Research, 1991
- Osteogenin promotes reexpression of cartilage phenotype by dedifferentiated articular chondrocytes in serum-free mediumExperimental Cell Research, 1991
- Growth-promoting effects of acidic and basic fibroblast growth factor on rabbit articular chondrocytes aging in cultureExperimental Cell Research, 1989
- A community effect in animal developmentNature, 1988
- Plasticity of the Differentiated StateScience, 1985
- Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gelsCell, 1982