Introduction: Although over 200 VCA including hand and face transplants have been performed worldwide with encouraging graft survival outcomes, long-term success with motor and sensory function return remains unpredictable. Optimizing nerve regeneration & function, and preventing denervation atrophy of target functional muscles are keys to achieving successful VCA outcomes. We investigated whether MSC therapy can improve sensory and motor functions. Methods: Lewis (RT1.A^l) rat was anesthetized and sciatic or individual sciatic nerve branches (tibial, peroneal and sural) of the right hind-limb were transected. After one hour the epineurium of the transected nerve ends were approximated by 10-O sutures. Mesenchymal stem cells (MSC; 5 x10⁶; passage ≤6) or vehicle (saline control) were administered locally and intravenously. Sensory (cutaneous pain reaction test) and motor (walking track analysis) functions were assessed at 1-2 week intervals following nerve repair. Results: Rat MSC expanded ex vivo were CD29+, CD90+, CD34-, CD31-, CD45low, MHC Class I+, and Class II-. MSC were pluripotent and differentiated in to adipocytes, osteocytes and chondrocytes in ex vivo cultures. At two week post nerve repair, total sensory nerve function (in sciatic or individual nerve repair models with or without MSC therapy) ranged from 1.1 to 1.3 on a scale of Grade 0-3 (0=No function; 3= Normal function). The sensory function improved gradually and by 12 weeks it was nearly normal (2.6 to 2.8) in all groups studied (n≥6 per group). Interestingly, peroneal sensory function appeared as early as one week (∼1) but not tibial or sural function. Onset of sensory function was slightly earlier in MSC treated groups but was not significant (P>0.05). At eight weeks post-individual nerve repair, the sciatic nerve function index (SFI) a measure of motor function (0 = normal function; -100 = nonfunctional) was -34 and – 77 in MSC and vehicle treated groups, respectively (n≥9); with sciatic nerve repair it was – 72 and – 92 in MSC and vehicle treated groups, respectively. Long-term motor function recovery (24 weeks) was apparent in MSC treated individual nerve repair model (SFI -63) but not in sciatic nerve repair model (SFI -100). Gastrocnemius muscle atrophy was lower (P<0.05) in individual nerve repair. Histology, cellular and molecular studies are ongoing. Conclusions: MSC therapy appears to promote both motor and sensory nerve function recovery in individual and sciatic nerve repair models.

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