Mesenchymal stem cell therapy to promote limb transplant functional recovery.

BACKGROUND: Limb transplantation is a viable option for reconstruction after traumatic limb loss; however, functional recovery can be suboptimal. The aim of this study was to determine whether mesenchymal stem cell (MSC) administration can improve limb transplant functional recovery.

METHODS: Orthotopic syngeneic hindlimb transplants were performed in Lewis rats, followed by topical and intravenous injections of syngeneic MSCs (5 × 106 ) or vehicle. Transplanted limb sensory and motor functions were tested by cutaneous pain reaction and walking track analysis, respectively.

RESULTS: MSCs expanded ex vivo were CD29+ , CD31- , CD34- , CD44+ , CD45low , CD90+ , MHC Class-I+ , Class-II- , and pluripotent. Greater than 90% of limb transplants survived. At 4 weeks post-transplantation, the mean sensory nerve (tibial, peroneal, or sural) function in MSC (n = 9) and vehicle (n = 9) groups was <0.3 on a scale of Grades 0-3 (0 = No function; 3 = Normal). By 8 weeks, the sensory scores for tibial, peroneal, and sural nerves were 2.2 ± 0.7, 1.2 ± 0.5, and 1.7 ± 0.9 in the vehicle, and 2.6 ± 0.4, 1.0 ± 0.9, and 1.7 ± 0.9 in the MSC group, respectively (n = 9/group). At 4, 8, 16, and 24 weeks, the overall sensory function was higher in MSC group (≥7/group). Sciatic Function Index (SFI), a measure of motor function, could not be calculated because of poor foot prints; therefore, a novel grading system was developed. Bone fusion/vascularization as determined by X-ray films/laser Doppler (≥2 week post-transplantation) were normal (n = 3/group). Gastrocnemius muscle was atrophied (P < 0.05), and flexion contractures were evident by 24 weeks.

CONCLUSIONS: Bone marrow-derived MSC therapy appears to improve sensory function recovery in a rat limb transplant model. Published 2016. This article is a U.S. Government work and is in the public domain in the USA Microsurgery 37:222-234, 2017.