Activin A expression regulates multipotency of mesenchymal progenitor cells.
BACKGROUND
Bone marrow (BM) stroma currently represents the most common and investigated source of mesenchymal progenitor cells (MPCs); however, comparable adult progenitor or stem cells have also been isolated from a wide variety of tissues. This study aims to assess the functional similarities of MPCs from different tissues and to identify specific factor(s) related to their multipotency.


METHODS
For this purpose, we directly compared MPCs isolated from different adult tissues, including bone marrow, tonsil, muscle, and dental pulp. We first examined and compared proliferation rates, immunomodulatory properties, and multidifferentiation potential of these MPCs in vitro. Next, we specifically evaluated activin A expression profile and activin A:follistatin ratio in MPCs from the four sources.


RESULTS
The multidifferentiation potential of the MPCs is correlated with activin A level and/or the activin A:follistatin ratio. Interestingly, by siRNA-mediated activin A knockdown, activin A was shown to be required for the chondrogenic and osteogenic differentiation of MPCs. These findings strongly suggest that activin A has a pivotal differentiation-related role in the early stages of chondrogenesis and osteogenesis while inhibiting adipogenesis of MPCs.


CONCLUSIONS
This comparative analysis of MPCs from different tissue sources also identifies bone marrow-derived MPCs as the most potent MPCs in terms of multilineage differentiation and immunosuppression, two key requirements in cell-based regenerative medicine. In addition, this study implicates the significance of activin A as a functional marker of MPC identity.
Djouad
Farida
F
Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, 9000 Rockville Pike, Bethesda, Maryland 20892, USA. farida.djouad@inserm.fr
Jackson
Wesley M
WM
Bobick
Brent E
BE
Janjanin
Sasa
S
Song
Yingjie
Y
Huang
George T J
GT
Tuan
Rocky S
RS
D028341:Activins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics*; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000235:genetics*; D003782:Dental Pulp / Q000166:cytology; D038681:Follistatin / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007165:Immunosuppression Therapy; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D009132:Muscles / Q000166:cytology; D010012:Osteogenesis / Q000235:genetics*; D014066:Palatine Tonsil / Q000166:cytology; D034622:RNA Interference; D034741:RNA, Small Interfering
D015415:Biomarkers; D038681:Follistatin; D034741:RNA, Small Interfering; C422405:activin A; D028341:Activins