title: Mesenchymal stem cell therapy to promote limb transplant functional recovery.
abstract: 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.
authors.affiliation: Department of Surgery, Madigan Army Medical Center, Tacoma, WA, 98431.
authors.forename: Emilie B
authors.initials: EB
authors.lastname: Fitzpatrick
authors.affiliation: Department of Clinical Investigation, Madigan Army Medical Center, Tacoma, WA, 98431.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Dehart
authors.affiliation: Department of Surgery, Madigan Army Medical Center, Tacoma, WA, 98431.
authors.forename: Tommy A
authors.initials: TA
authors.lastname: Brown
authors.affiliation: Department of Clinical Investigation, Madigan Army Medical Center, Tacoma, WA, 98431.
authors.forename: Shashikumar K
authors.initials: SK
authors.lastname: Salgar
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D006085:Graft Survival; D006614:Hindlimb / Q000601:surgery* / Q000637:transplantation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D019651:Plastic Surgery Procedures / Q000379:methods*; D020127:Recovery of Function; D014945:Wound Healing / Q000502:physiology*