Chemically Extracted Acellular Nerve Allograft Seeded with SDNF and Autogenic ADSCs for Peripheral Nerve Repairment in a Beagle Model

Abstract

Peripheral nerve repair is a major challenge in clinical practice. Nerve grafting is required to treat severe peripheral nerve defects caused by injuries. Available nerve sources for autologous transplantation are limited. Stem cells offer promise for peripheral nerve repair and regeneration. However, the current lack of Schwann cell phenotype, high costs, and major trauma limit the production of Schwann cells from stem cell differentiation. Thus, the purpose of this study is to investigate the ability of adipose-derived stem cells (ADSCs) to differentiate into the Schwann cell phenotype, after treatment with Schwann cell-derived neurotrophic factor (SDNF) in vitro. ADSCs were isolated and cultured for use in two types of nerve grafts: Acellular allogeneic nerves (ACEN), and acellular allogeneic nerves treated with SDNF (ACEN + SDNF). Chemically extracted, untreated acellular allogeneic nerves (CEN), acellular allogeneic nerves with isolated and cultured autologous SCs (CEN + SCs), and fresh autografts (AG) served as controls. Hematoxylin and eosin (HE) and S100 immunohistochemical staining were performed to observe the cytokine levels in the nerve grafts; enzyme-linked immunosorbent assay (ELISA) and realtime PCR were performed to evaluate the S100 and glial fibrillary acidic protein (GFAP) expression. The acellular nerve allografts seeded with ADSCs and SDNF showed significant S100 and GFAP expressions. No significant statistical differences were observed between the ACEN + SDNF, ACEN + SCs, and AG groups. These data suggest that such acellular nerve allografts should be evaluated as therapeutic strategies for treating severe peripheral nerve defects.