Adipose-derived stem cells protect against endoneurial cell death: Cell therapy for nerve autografts.

Abstract

One of the major problems with nerve grafts is that the survival of a graft segment, including endoneurial Schwann cells (SCs), is uncertain. We investigated whether the survival of nerve grafts is improved when adipose-derived stem cells (ASCs) are incorporated into the grafts. To examine the cell-protective effects of ASCs on SCs in vitro, we used an indirect coculture system. In vivo effects of the incorporation of ASCs into grafts were examined using a graft model in the rat common peroneal nerve. Grafts were entubulated to isolate them from the surrounding tissues, mimicking the clinical conditions of a poorly vascularized recipient bed. Thirty-six Lewis rats were divided into three groups, i.e., nerve graft only, entubulated nerve graft, and entubulated nerve graft + ASC transplantation. In each group, four rats and eight rats were used for short-term (10 days) and long-term (12 weeks) follow-up study, respectively. After 24 hours of serum deprivation, the numbers of 7-aminoactinomycin D, and TUNEL-positive SCs significantly decreased when indirectly cocultured with ASCs (P < 0.01). When ASCs were transplanted to the epineurial layer of the grafts, the number of endoneurial TUNEL-positive cells decreased significantly, as compared with grafts without ASCs, at 10 days postoperatively (P < 0.05). Postoperative walking track analysis showed that the ASC-transplanted grafts showed significantly faster function recovery, as compared with grafts without ASCs (P < 0.05). These results suggest that nerve autografts + ASC therapy could offer a new approach to obtaining optimal outcomes after peripheral nerve injury.