Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation
Final rept. 20 Sep 2011-20 Jul 2012
JOHNS HOPKINS UNIV BALTIMORE MD
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BACKGROUND Combat wounds have unique features including significant devitalization due to high-energy blast, deep contamination, complexcomposite tissue loss, and multiple coexisting injuries. In this regard, Composite Tissue Allotransplantation CTA is an innovative reconstructive modality that can provide functional restoration after complex musculoskeletal trauma. CTA is now a clinical reality with numerous upper extremity and face transplants performed worldwide thus providing new hope for service members suffering from catastrophic combat trauma and devastating tissue defects. Broader clinical application of CTA, however, continues to be hampered by requirement for long-term multi-drug immunosuppression to prevent graft rejection. This study for the first time proposes a novel cell-based therapy utilizing Mesenchymal Stem Cells MSC that augments nerve regeneration while minimizing the need for immunosuppression. METHODS Sciatic nerve transections and repairs were performed on Lewis rats in control and experimental groups with local and systemic intravenous MSC injection n8 per group. Syngeneic Lewis-Lewis and Allogeneic Lewis-Brown Norway hind limb transplants were performed to analyze neuroregenerative effects of MSC with and without allo-immune response n4 per group. RESULTS Compound Muscle Action Potential CMAP amplitudes significantly improved for systemic MSC injection groups relative to controls after sciatic nerve transection and repair. However, no significant differences were observed between groups in functional gait analysis. In addition, histomorphometry and gastrocnemius weight data did not indicate any significant differences among groups. However, the number and density of axons observed between 6 and 16 weeks increased by approximately 35 and 30, respectively. Syngeneic hind limb transplants that received local or systemic MSC injections showed significant enhancement of functional recovery following MSC therapy.
- Anatomy and Physiology
- Medicine and Medical Research