Conditional TGF-β(1) treatment increases stem cell-like cell population in myoblasts

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)-β(1). Our results show that a lower concentration of TGF-β(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-β(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-β(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-β(1) were also observed in the primary myoblasts of mice. Our results suggest that TGF-β(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.