Ghrelin and adipose-derived mesenchymal stromal cells improve nerve regeneration in a rat model of epsilon-caprolactone conduit reconstruction

Objective. Attempts have been made to improve nerve conduits in peripheral nerve reconstruction. We investigated the potential therapeutic effect of adipose-derived mesenchymal cells (ASCs) and ghrelin (GHR), a neuropeptide with neuroprotective, trophic, and developmental regulatory actions, on peripheral nerve regeneration in a model of severe nerve injury repaired with nerve conduits. Material and methods. The right sciatic nerves of 24 male Wistar rats were 10-mm transected unilaterally and repaired with Dl-lactic-epsilon-caprolactone conduits. Rats were then treated locally with saline, ASCs, or GHR. At 12 weeks post-surgery, we assessed limb function by measuring ankle stance angle and percentage muscle mass reduction and evaluated the histopathology, immunohistochemistry, ultrastructure, and morphometry of myelinated fibers. Main Results. Rats receiving GHR or ASCs showed no significant increased functional recovery in ankle stance angle (p=0.372) but a higher nerve area (p=0.015), myelin area (p=0.046) and number of myelinated fibers (p=0.012) in the middle and distal segments of operated sciatic nerves in comparison to saline-treated control animals. Conclusion. These results suggest that utilization of ghrelin or ASCs may improve nerve regeneration using Dl-lactic-epsilon-caprolactone conduits.The authors would especially like to acknowledge the contribution to the histochemical and immunohistochemical studies of Serafin Velez Garcia and Carmen Ruiz Guzman, technicians in the Surgical Department, and Maria Dolores Rodriguez, in the Pathology Department and IBIMER of Granada University. This investigation was supported in part by Research Group #CTS-138 (Junta de Andalucia, Spain).Peer reviewe