Stem cell therapy to promote sensory and motor nerve function recovery in a limb transplant model (TRAN3P.863)

Abstract

Abstract Introduction: Hand and leg transplantation (Tx) in military/civilian populations is increasingly needed to improve the quality of life. Our objective was to investigate whether Mesenchymal Stem Cell (MSC) therapy can improve nerve regeneration and function. Methods: We performed orthotopic syngeneic hind-limb transplants in Lewis (RT1.Al) rats. Following Tx rats received syngeneic MSC (5x106; passage ≤8) or vehicle intravenously and locally. Results: Ex vivo expanded Rat MSCs were CD29+, CD31-, CD34-, CD44+, CD45low, CD90+, MHC Class I+, Class II- and pluripotent. Limb Tx was highly successful (100% survival). Four weeks post-Tx sensory nerve function (determined by cutaneous pain reaction) was <0.3 on a scale of Grade 0 to 3 (0=No function; 3=Normal function). By 8 weeks in vehicle group it was 2.2±0.7(tibial), 1.2±0.5(peroneal) and 1.7±0.9 (sural), and in MSC group it was 2.6±0.4(tibial),1.0±0.9(peroneal) and 1.7±0.9(sural). Overall sensory function was higher but not significant in MSC group compared to vehicle group at 4, 8, 16 and 24 weeks post-Tx. Walking track analysis (for motor nerve function) did not produce clear foot prints to calculate Sciatic Function Index (SFI), so a novel grading system was developed. Gastrocnemius muscle was atrophied (P<0.05) and animals developed flexion-contractures in the transplanted limb. Conclusion: The limb Tx procedure was highly successful, sensory function was recovered (>70%) and MSCs appear to promote nerve function recovery.