Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 15, Issue 3, Pages 679-690Publisher
WILEY
DOI: 10.1111/j.1582-4934.2010.01042.x
Keywords
TGF-beta(1); dedifferentiation; skeletal muscle; stem cell; multipotency
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Funding
- NIH
- DOD
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The limitation in successfully acquiring large populations of stem cell has impeded their application. A new method based on the dedifferentiation of adult somatic cells to generate induced multipotent stem cells would allow us to obtain a large amount of autologous stem cells for regenerative medicine. The current work was proposed to induce a sub-population of cells with characteristics of muscle stem cells from myoblasts through conditional treatment of transforming growth factor (TGF)-beta(1). Our results show that a lower concentration of TGF-beta(1) is able to promote C2C12 myoblasts to express stem cell markers as well as to repress myogenic proteins, which involves a mechanism of dedifferentiation. Moreover, TGF-beta(1) treatment promoted the proliferation-arrested C2C12 myoblasts to re-enter the S-phase. We also investigated the multi-differentiation potentials of the dedifferentiated cells. TGF-beta(1) pre-treated C2C12 myoblasts were implanted into mice to repair dystrophic skeletal muscle or injured bone. In addition to the C2C12 myoblasts, similar effects of TGF-beta(1) were also observed in the primary myoblasts of mice. Our results suggest that TGF-beta(1) is effective as a molecular trigger for the dedifferentiation of skeletal muscle myoblasts and could be used to generate a large pool of progenitor cells that collectively behave as multipotent stem cell-like cells for regenerative medicine applications.
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