Research
Activin A expression regulates multipotency of mesenchymal progenitor cells
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* Corresponding author: Farida Djouad farida.djouad@inserm.fr
1 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
2 Current address: Inserm U 844, Hôpital Saint-Eloi, Bâtiment INM, 34295 Montpellier, France
3 Current address: Department of Biological Sciences, 2500 University Drive NW, Calgary, Alberta, T2N 1N4, Canada
4 Current address: Department of Otorhinolaryngology, Head & Neck Surgery, Zagreb Clinical Hospital Centar, Zagreb University School of Medicine, Salata 4, 10000 Zagreb, Croatia
5 Current address: Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, 72 East Concord Street, Boston, MA 02118, USA
6 Current address: Department of Orthopaedic Surgery, Center for Cellular and Molecular Engineering, University of Pittsburgh School of Medicine, 450 Technology Drive, Room 221, Pittsburgh, PA 15219, USA
Stem Cell Research & Therapy 2010, 1:11 doi:10.1186/scrt11
Published: 4 May 2010Abstract
Introduction
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.