Stem cell therapy improved nerve regeneration and functional outcomes in vascularized composite allotransplantation 2258692

Abstract

Abstract Introduction Vascularized composite allotransplantation (VCA) includes limb and face transplants an emerging field to improve the quality of life of limb amputees. We investigated whether adult bone marrow derived mesenchymal stem cell (MSC) therapy can improve functional outcomes in limb transplantation (Tx). Methods We performed orthotopic syngeneic hind-limb Tx in Lewis rats (n = 5/group). MSC (2 million; passage ≤6) or vehicle was administered locally and intravenously. Sensory function (SF) and motor function (MF) of the Tx limb was assessed weekly. At the study endpoint (16 weeks) rats were euthanized and limb tissues were harvested for cell/molecular analysis. Results Total SF recovery (on a scale of Grade 0-3) improved from 1.4 in 8 weeks to 2.6 by week 16. SF in the tibial and peroneal nerve boundaries recovered by ∼5 weeks. MF (on a scale of Grade 0-4) improved (P < 0.05) with MSC compared to control by week 16 (Grade 2.6 Vs 0.6). Gastrocnemius muscle was atrophied (P < 0.05) and rats developed mild flexion-contractures in MSC treated rats (Grade 0.9) compared to untreated control rats (Grade 1.6) on a scale of 0-3. Rat MSCs were CD29+, CD44+, CD90+, MHC Class-I+, CD31-, CD34-, MHC Class II-; and multi-potent. Immuno histochemistry showed increased (P < 0.05) expression of nerve regeneration markers (NF-M, S100, Oct6, Krox20/EGR2, GAP43) in the sciatic nerve of MSC treated rats compared to controls. Conclusion MSC therapy improved limb transplant functional recovery and is attributed to improved nerve regeneration and muscle innervation. Funding Source CDMRP-DoD Topic Categories Transplantation Immunology (TRAN)