Differentiated adipose-derived stem cells promote myelination and enhance functional recovery in a rat model of chronic denervation

Transplantation of autologous Schwann cells (SCs) is a promising approach for treating various peripheral nerve disorders, including chronic denervation. However, given their drawbacks, such as invasive biopsy and lengthy culture in vitro, alternative cell sources would be needed. Adipose-derived stem cells (ASCs) are a candidate, and in this study rat ASCs transdifferentiated into a SC phenotype (dASC) cocultured with dorsal root ganglion neurons were shown to associate with neurites and to express myelin basic protein (MBP)-positive myelin protein. Furthermore, dASCs transplanted into a chronically denervated rat common peroneal nerve survived for at least for 10 weeks, maintaining their differentiated state. Immunohistochemical analysis revealed that transplanted dASCs associated with regenerating axons, forming MBP-/protein zero-positive myelin sheaths. The cell survival and myelin expression assessed by double labelling with S100 and glial fibrillary acidic protein were similar between the dASC- and SC-transplanted nerves. Importantly, transplantation of dASCs resulted in dramatically improved motor functional recovery and nerve regeneration, with a level comparable to, or even superior to, transplantation of SCs. In conclusion, dASCs are capable of myelinating axons in vivo and enhancing functional outcome after chronic denervation.