Mesenchymal stem cells in a polycaprolactone conduit enhance median-nerve regeneration, prevent decrease of creatine phosphokinase levels in muscle, and improve functional recovery in mice

Abstract

Although the majority of peripheral-nerve regeneration studies are carried out on the sciatic nerve, lesions of the upper extremities are more common in humans and usually lead to significant physical disabilities. The present study was driven by the hypothesis that a combination of strategies, namely grafts of mesenchymal stem cells (MSC) and resorbable polycaprolactone (PCL) conduits would improve median-nerve regeneration after transection. Mouse median nerves were transected and sutured to PCL tubes that were filled with either green fluorescent protein (GFP+) MSC in DMEM or with DMEM alone. During the post-operative period, animals were tested weekly for flexor digitorum muscle function by means of the grasping test. After 8 weeks, the proximal and middle portions of the PCL tube and the regenerating nerves were harvested and processed for light and electron microscopy. The flexor digitorum muscle was weighed and subjected to biochemical analysis for creatine phosphokinase (CK) levels. Scanning electron microscopy of the PCL tube 8 weeks after implantation showed clear signs of wall disintegration. MSC-treated animals showed significantly larger numbers of myelinated and unmyelinated nerve fibers and blood vessels compared with DMEM-treated animals. The flexor digitorum muscle CK levels were significantly higher in the MSC-treated animals, but muscle weight values did not differ between the groups. Compared with the DMEM-treated group, MSC-treated animals showed, by the grasping test, improved functional performance throughout the period analyzed. Immunofluorescence for S-100 and GFP showed, in a few cases, double-labeled cells, suggesting that transplanted cells may occasionally transdifferentiate into Schwann cells. Our data demonstrate that the polycaprolactone conduit filled with MSC is capable of significantly improving the median-nerve regeneration after a traumatic lesion.