Bridging small-gap peripheral nerve defects using acellular nerve allograft implanted with autologous bone marrow stromal cells in primates

Abstract

This study evaluated the effects of the transplantation of a tissue-engineered nerve derived from an acellular allogenic nerve graft, combined with autologous bone marrow stromal cells (MSCs), into peripheral nerve defects. In a rhesus monkey model, nerve regeneration was evaluated across a 1-cm lesion in the radial nerve by using an acellular allogenic nerve injected with autologous MSCs. Simple acellular nerve allografts served as control. Eight weeks after surgery, immunofluorescence staining, histologic morphometrical analysis and electrophysiologic evaluation were performed. Fluorescence microscopy revealed that some MSCs were immunopositive to S-100 protein, indicating a Schwann cell (SC) phenotype. The group treated with cultured MSCs showed a statistically higher number of nerve fibers, with well-shaped remyelinated axons. The motor conduction velocities and the peak amplitudes of compound muscle action potentials (CMAP) for the group treated with MSCs were higher than those of the controls. This outcome indicated that MSCs are able to differentiate into Schwann-like cells in vivo and to promote nerve regeneration in primates. Furthermore, the acellular nerves injected with MSCs provided a favorable environment for the growth and myelination of regenerating axons when compared to acellular nerves alone.