Stem cell and novel biologic therapies to enhance functional recovery in vascular composite allotransplantation (TRAN1P.922)

Abstract

Abstract Introduction: Vascular composite allotransplantation (VCA) such as limb and face require successful nerve regeneration and reinnervation of graft motor and sensory targets for optimal clinical outcome. Methods: Lewis (RT1.Al) rat was anesthetized and individual sciatic nerve branches (tibial, peroneal and sural) of the right hind-limb were transected. After one hour the epineurium of the transected nerves were approximated by 10-O sutures. Mesenchymal Stem Cells (MSC; 5x106; passage ≤6), G-CSF (50 µg/kg), Dihexa (2 mg/kg) or Vehicle were administered locally and intravenously. Results: Rat MSC expanded ex vivo were CD29+, CD90+, CD34-, CD31-, CD45low, MHC Class I+, and Class II-; and were pluripotent. At two weeks post nerve repair, total sensory nerve function in all groups was ~1.5 on a scale of Grade 0-3 (0=No function; 3=Normal function). By 8 weeks sensory function was ≥ 2.5 in all groups studied (n≥6); slightly lower in the vehicle group. Peroneal sensory function appeared as early as one week (≥2) but not tibial or sural function (~0.5). At five weeks, the sciatic nerve function index (SFI) a measure of motor function (0=Normal function; -100=Nonfunctional) was ~ -50 in G-CSF, and ~ -80 in MSC, Dihexa, and Vehicle treated groups (n≥6). By 12 weeks SFI in G-CSF group was markedly improved (-25). Histology and molecular studies are ongoing. Conclusions: MSC and G-CSF appear to promote both sensory and motor nerve functions in nerve transection repair model.