Conditional TGF-β1 treatment increases stem cell-like cell population in myoblasts.
Bottom Line: The limitation in successfully acquiring large populations of stem cell has impeded their application.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.
Affiliation: The Laboratory of Molecular Pathology, Stem Cell Research Center, Children's Hospital of UPMC, Pittsburgh, PA, USA.Show MeSH
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Mentions: The source of muscle ‘precursors’ during the muscle healing process has been suggested include activated satellite cells, locally released muscle stem cells, circulating haematopointic and bone marrow cells. However, the natural muscle healing process from injuries or diseases (i.e. Duchenne muscular dystrophy/DMD) often leads to the excessive formation of fibrotic scar tissue, in which case stem cell-based therapies can be helpful for improved regeneration [2, 5, 55, 56]. Compared to the time-consuming isolation of a limited number of muscle stem cells and in vitro propagation, the induction of stem cells from homogenous myoblasts could be a much more efficient way to obtain enough cells with multi-differentiation potentials for transplantation and tissue engineering . In the current experiment, we discovered that after conditional TGF-β1 stimulation in vitro, myoblasts demonstrated an increased expression of stem cell markers and an increased ability for S-phase re-entry. Moreover, these stem cell-like cells generated by the TGF-β1 pre-treatment, which may not be identical to endogenous muscle stem cells but carry many characteristics of muscle stem cells, were shown to have improved regenerative capacities in vivo in effectively repairing both dystrophic muscle and injured bone. In addition to the specific cell line of C2C12 myoblasts, similar effects of TGF-β1 were also observed with primary myoblasts isolated from mice (Fig. 6). This suggests that TGF-β1 is generally functional in increasing the number of stem cell-like cells when applied to skeletal muscle myoblasts. The representative mechanism suggested for our results is proposed as Figure 7.
Affiliation: The Laboratory of Molecular Pathology, Stem Cell Research Center, Children's Hospital of UPMC, Pittsburgh, PA, USA.