Immunologist/Physiologist/ Professor of Surgery Madigan Army Medical Center Tacoma, Washington, United States
Disclosure(s):
Shashikumar Salgar, PhD: No financial relationships to disclose
Introduction/Rationale: 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. Immunohistochemistry 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.
