Bone marrow derived mesenchymal stem cell therapy to improve nerve regeneration and function in a rat limb transplant model (P2170)

Abstract

Abstract Introduction: Preventing immune rejection and optimizing nerve regeneration are keys to successful outcomes in hand and limb transplantation (Tx). Our objective was to investigate whether MSC can improve nerve regeneration and function. Methods: Orthotopic syngeneic right hind-limb transplants were performed in Lewis (RT1.Al) rats. Limb recipient rats received syngeneic MSC (5 x106; passage ≤7) or vehicle (saline) locally around nerve, bone and vascular anastamoses sites, and 5x106 MSC intravenously. Results: Rat MSC expanded ex vivo were CD29+, CD90+, CD34-, CD31-, CD45low, MHC Class I+, Class II-, CD80low, and CD86-. MSC used were pluripotent and differentiated in to adipocytes, osteocytes and chondrocytes in ex vivo cultures under specific conditions. At six weeks post-Tx, walking track analysis did not produce clear foot prints to calculate Sciatic Function Index (SFI). However, by six weeks cutaneous pain reaction test demonstrated sensory nerve function; on a scale of Grade 0-3 (0=No function; 3= Normal function) in vehicle treated animals (n=5) it was 2.1±1.3 (tibial), 0.8±0.7 (peroneal) and 1.2±01.0 (sural), and in MSC treated animals (n=5) it was 1.3±1.1 (tibial), 1.2±1.2 (peroneal) and 1.4±0.8 (sural). Laser doppler analysis revealed normal vascularization and limb transplant survival was >95%. Conclusion: The limb transplant procedure was highly successful and awaiting data on long-term effects of MSC therapy which appears to promote functional recovery.