Abstract
Muscle-derived stem cells (MDSCs) are multipotent stem cells with a remarkable long-term self-renewal and regeneration capacity. Here, we show that postnatal MDSCs could be transdifferentiated into Schwann cell-like cells upon the combined treatment of three neurotrophic factors (PDGF, NT-3 and IGF-2). The transdifferentiation of MDSCs was initially induced by Schwann cell (SC) conditioned medium. MDSCs adopted a spindle-like morphology similar to SCs after the transdifferentiation. Immunocytochemistry and immunoblot showed clearly that the SC markers S100, GFAP and p75 were expressed highly only after the transdifferentiation. Flow cytometry assay showed that the portion of S100 expressed cells was more than 60 percent and over one fourth of the transdifferentiated cells expressed all the three SC markers, indicating an efficient transdifferentiation. We then tested neurotrophic factors in the conditioned medium and found it was PDGF, NT-3 and IGF-2 in combination that conducted the transdifferentiation. Our findings demonstrate that it is possible to use specific neurotrophic factors to transdifferentiate MDSCs into Schwann cell-like cells, which might be therapeutically useful for clinical applications.
Highlights
Schwann cells (SCs) play a crucial role in peripheral nerve development and regeneration, and are an attractive therapeutic target in peripheral nerve injuries [1,2,3]
To further demonstrate that the PP6 cells were Muscle-derived stem cells (MDSCs), we investigated the expression of Sca1 which was a well-defined marker for putative MDSCs in PP6 cells
These results suggested that the PP6 cells isolated from mouse skeletal muscles were highly purified MDSCs
Summary
Schwann cells (SCs) play a crucial role in peripheral nerve development and regeneration, and are an attractive therapeutic target in peripheral nerve injuries [1,2,3]. It is reported that cultured SCs could induced neuronal sprouting and regrowth in cell culture experiments and improve peripheral nerve regeneration in vivo [4,5]. SCs can be obtained from nerve biopsies for autologous transplantation and will not elicit an intense immune response. It’s difficult to culture sufficient numbers of autologous SCs because of their restricted mitotic activity, and there are other disadvantages such as limitations in the supply of nerve material [6,7]. Stem cells may be an alternative source for SCs. the clinical application of embryonic stem cells is limited because of ethical problems and their carcinogenic potential [8]. Increase evidence shows that adult stem cells may be promising candidate sources of cells [9,10]
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