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Robustness Testing of Mesenchymal Stem Cell Monotherapy Following Vascularized Composite Allotransplantation.
Steinberger, Zvi; Xu, Heng; Kazmers, Nikolas H; Chen, Chi-Der; Caron, Robert J; Qin, Ling; Zhang, Yixin; Levin, Lawrence Scott.
Afiliación
  • Steinberger Z; Department of Orthopedics Surgery, Penn Medicine University City, Philadelphia, Pennsylvania.
  • Xu H; Department of Orthopedic Surgery, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
  • Kazmers NH; Department of Orthopedics Surgery, Penn Medicine University City, Philadelphia, Pennsylvania.
  • Chen CD; Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai, China.
  • Caron RJ; Department of Orthopaedic Surgery, University of Utah, Salt Lake City, Utah.
  • Qin L; Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
  • Zhang Y; Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.
  • Levin LS; Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.
J Reconstr Microsurg ; 36(6): 397-402, 2020 Jul.
Article en En | MEDLINE | ID: mdl-32040964
BACKGROUND: Immunosuppression risks are a major concern with vascularized composite allotransplantation (VCA). As an emerging strategy, the antirejection role played by mesenchymal stem cells (MSCs) is receiving attention. However, the current literature reports are inconclusive regarding the robustness of the MSC monotherapy. Using a rat forelimb VCA model, this study tested the robustness of the immunomodulation efficacy of gingival-derived MSCs (GMSCs) and bone marrow-derived MSCs (BMMSCs). METHODS: Forelimbs were transplanted on pairs of major histocompatibility complex-incompatible rats (Wistar-Kyoto donor, Lewis [LEW] recipient). Twenty-four LEW rats were randomly divided into four groups, including control (no treatment) and three treatment groups: rapamycin (2 mg/kg/day for 28 days, postoperatively), BMMSC and GMSC, both of which received donor-derived stem cells administered intravenously on postoperative days (PODs) 0, 3, 7, and 14. Rejection was considered as 80% skin necrosis of the allograft. Microcomputed tomography (µCT) was performed to evaluate healing at osteosynthesis site. On POD 14, limbs from each group underwent histological analysis and rejection grading using the Banff system. RESULTS: Both BMMSC (15.0 days) and GMSC (14.7 days) treatment failed to prolong VCA survival in comparison with the control group (13.8 days; p > 0.050), while the rapamycin significantly delayed acute VCA rejection (24.5 days; p = 0.003). Micro-CT imaging revealed no gross visual difference across all groups. Histology revealed that the control group was most severely affected (grades III and IV) followed by MSC (grade II) and rapamycin (grade I). CONCLUSION: MSC monotherapy, both BMMSC and GMSC, did not inhibit rejection in our VCA model. Skin immunogenicity is an important issue in promoting rejection, and a concomitant immunosuppression regimen should be considered to prolong allograft survival.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Mesenquimatosas / Alotrasplante Compuesto Vascularizado Límite: Animals Idioma: En Revista: J Reconstr Microsurg Asunto de la revista: NEUROCIRURGIA Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Mesenquimatosas / Alotrasplante Compuesto Vascularizado Límite: Animals Idioma: En Revista: J Reconstr Microsurg Asunto de la revista: NEUROCIRURGIA Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos