Grant: Project Grant

Peripheral nerve injuries occur in approximately 2% of trauma patients. Some nerve injuries recover spontaneously, but for most patients, functional recovery is unsatisfactory. For nerve injuries resulting in a gap defect, current clinical management involves harvesting a donor nerve to bridge the gap which unfortunately can create significant problems at the donor site. An alternative approach is to use artificial conduit coupled with cell therapy such as Schwann cells (SCs), the resident glia in the peripheral nerve. Unfortunately, harvesting SCs from an undamaged nerve for transplant will cause additional neurologic dysfunction. To overcome this hurdle, we have previously shown that human SCs harvested from skin are essentially identical to SCs from nerve, raising the hope that only a small skin biopsy is required to generate SCs for nerve repair. Before such treatment can reach the clinic, skin-derived SCs need to be more reliably expanded to therapeutic numbers and be proven to show effectiveness in a clinically relevant large animal model. Therefore, the goals of our proposal are: 1) to use bioengineering approaches to expand the population of SCs in computer-controlled bioreactors and to establish a robust, reliable, and reproducible protocol; 2) to use pig's own skin-derived SCs in a pig nerve injury model, which closely resembles human nerve repair; and ultimately, 3) to study the human skin-derived SCs in immuno-suppressed pig nerve injury model, focusing on how these cells modify the local environment and influence functional outcomes. We expect to show that augmenting grafts with these cells will improve functional outcome. We are the first group to successfully isolate and purify these skin-derived SCs from human tissue, and they hold great promise in cell therapy; not only in nerve repair, but also in other neurological diseases. The proposed study will provide scientific evidence for the future use of these cells in clinical trials.