Differentiated adipose-derived stem cells promote the recovery of nociceptor function in rats.

The loss of nociceptive function in the skin because of trauma or surgery can impair the quality of life. The recovery of nociceptor function is mediated by two different axonal responses: nerve growth factor (NGF)-dependent collateral sprouting of undamaged nerves and NGF-independent regeneration of damaged nerves. We reported previously that adipose-derived stem cells (ASCs) can transdifferentiate into Schwann cell (SC)-like cells (dASCs) and that transplantation of dASCs increases axonal density in skin flaps. In the present study, we used an animal model that allowed for the individual assessment of collateral sprouting and regeneration. In-vitro differentiation of ASCs to dASCs significantly increased the production of NGF and brain-derived neurotrophic factor (BDNF) to levels comparable with SCs. In-vivo experiments showed that dASC and SC transplantation significantly increased the area of the mechano-nociceptive field in both collateral sprouting and regeneration models, whereas ASC transplantation exerted no significant effect. Antibody blocking experiment showed that these effects of dASC transplantation in the regeneration model were partly mediated by BDNF. Interestingly, the final areas of nociceptive fields between the two experimental models did not differ significantly for any treatment condition. These results indicate that dASC transplantation differentially facilitates collateral sprouting and axonal regeneration by delivering NGF and other neurotrophic factors (e.g. BDNF), respectively. Although there is a limit to nociceptive field enlargement irrespective of axonal response, dASC transplantation could present a new approach for improving nociceptive function in denervated skin.