Introduction: Hand and leg transplantation (Tx) in military and civilian populations is increasingly needed to improve the quality of life of individuals. Optimizing nerve regeneration is a key to successful outcomes. The objective of this study was to investigate whether Mesenchymal Stem Cells (MSC) derived from bone marrow can improve nerve regeneration and functional outcome in a limb transplant model.
Methods: Orthotopic syngeneic right hind-limb transplants were performed in Lewis (RT1.Al) rats. The donor and recipient femoral artery/vein were anastamosed by Vascular Cuff method, and the sciatic nerve (epineurium) and muscles were approximated by suturing. The femur was stabilized with a stainless steel pin and bone cement. Animals received MSC (5 x106; passage ≤7) or vehicle (saline control) locally around nerve, bone and vascular anastamoses sites, and 5×106 MSC intravenously on the day of surgery. Intravenous MSC or vehicle injections were repeated every week for four weeks. Walking track and cutaneous pain reaction tests were performed at 1-2 week intervals post-Tx.
Results: MSC isolated from Lewis rat bone marrow and expanded ex vivo were CD29+, CD90+, CD34–, CD31–, CD45low, MHC Class I+, Class II–, CD80low, and CD86–. MSC were confirmed for pluripotency based on their differentiation potential in to adipocytes, osteocytes and chondrocytes in ex vivo cultures under specific conditions. At four weeks post-Tx, no animal bore complete weight on the transplanted limb, and we were not able to obtain clear foot prints to calculate Sciatic Function Index (SFI). However, 2 out of 5 vehicle treated animals and 1 out of 2 MSC treated animals showed slight foot prints by 2 weeks, which became more recognizable by 4 weeks. Also, 3 out of 5 control animals were Grade 1-2 on a scale of 0-3 (0=No Function; 3= Normal function) for peroneal, tibial and / or sural nerve sensory function at 4-6 weeks. In our pilot study (n=5) without MSC or vehicle therapy the sensory nerve function was Grade 1.53±0.69 (peroneal), Grade 1.79±0.29 (tibial) and Grade 1.39±0.55 (sural) at ∼8 weeks. Laser doppler analysis revealed normal vascularization in transplanted limbs. Limb transplant survival was 100%. The study is ongoing and awaiting data on long-term effects of MSC on neurogenesis, angiogenesis, myogenesis and limb function.
Conclusion: The limb transplant procedure was highly successful and MSC therapy appears to promote nerve functional recovery in our limb transplant model.
To cite this abstract in AMA style:Fitzpatrick E, DeHart M, Tercero J, Brown T, Salgar S. Mesenchymal Stem Cell Therapy To Promote Functional Recovery in a Limb Transplant Model [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/mesenchymal-stem-cell-therapy-to-promote-functional-recovery-in-a-limb-transplant-model/. Accessed May 7, 2021.
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