Respective stemness and chondrogenic potential of mesenchymal stem cells isolated from human bone marrow, synovial membrane, and synovial fluid

Paul Neybecker (1) , Christel Henrionnet (1) , Elise Pape (1, 2) , Laurent Grossin (1) , Didier Mainard (1, 3) , Laurent Galois (1, 3) , Damien Loeuille (1, 4) , Pierre Gillet (1, 2) , Astrid Pinzano (1, 4)

1 IMoPA - Ingénierie Moléculaire et Physiopathologie Articulaire
2 Service de Pharmacologie Clinique et Toxicologie [CHRU Nancy]
3 COTA - Service de Chirurgie Orthopédique, Traumatologique et Arthroscopique [CHRU Nancy]
4 Service de Rhumatologie [CHRU Nancy]

Background: MSCs isolated from bone marrow (BM-MSCs) have well-established chondrogenic potential, but MSCs derived from the synovial membrane (SM-MSCs) and synovial fluid (SF-MSCs) are thought to possess superior chondrogenicity. This study aimed to compare the in vitro immunophenotype and trilineage and chondrogenic potential of BM-MSCs to SM-MSCs and SF-MSCs. Methods: MSCs were isolated from bone marrow (BM-MSCs), synovial membrane (SM-MSCs), and synovial fluid (SF-MSCs) extracted from the hips (BM) and knees (SM and SF) of advanced OA patients undergoing arthroplasty. Flow cytometric analysis was used at P2 to evaluate cell stemness. The trilinear differentiation test was performed at P2. At P3, MSC-seeded collagen sponges were cultured in chondrogenic medium for 28 days. Chondrogenic gene expression was quantified by qRT-PCR. Finally, the implants were stained to assess the deposition of proteoglycans and type II collagen. Results: Despite variability, the immunophenotyping of BM-MSCs, SM-MSCs, and SF-MSCs was quite similar. All cell types were positive for the expression of stem cell markers and negative for exclusion markers. Additionally, chondrogenic differentiation and hypertrophy were more pronounced in BM-MSCs (ACAN, SOX9, COL2B, and COL10A) than in SF-MSCs, with SM-MSCs having intermediate characteristics. Concerning matrix synthesis, the three cell types were equipotent in terms of GAG content, while BM-MSC ECM synthesis of type II collagen was superior. Conclusions: Chondrogenic MSCs are easily collected from SM and SF in advanced human OA, but in vitro chondrogenesis that is superior to age-matched BM-MSCs should not be expected. However, due to intra-articular priming, SF-MSCs did not overexpress hypertrophic gene.

Mots clés: Mesenchymal stromal stem cells; Cartilage engineering; Synovial membrane; Synovial fluid; Bone marrow; Chondrogenic differentiation; Growth factors

Domaines: Biologie cellulaire; Biotechnologies

Paul Neybecker, Christel Henrionnet, Elise Pape, Laurent Grossin, Didier Mainard, et al.. Respective stemness and chondrogenic potential of mesenchymal stem cells isolated from human bone marrow, synovial membrane, and synovial fluid. Stem Cell Research and Therapy, 2020, 11, pp.316. ⟨10.1186/s13287-020-01786-5⟩. ⟨hal-02929893⟩