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Use of FK506 and bone marrow mesenchymal stem cells for rat hind limb allografts
Authors:Youxin Song  Zhujun Wang  Zhixue Wang  Hong Zhang  Xiaohui Li  Bin Chen
Institution:Youxin Song (Department of Orthopedics, Affiliated Hospital of Chengde Medical College, Chengde 067000, Hebei Province, China);Zhujun Wang (Department of Research, Affiliated Hospital of Chengde Medical College, Chengde 067000, Hebei Province, China);Zhixue Wang (Department of Anesthesia, Affiliated Hospital of Chengde Medical College, Chengde 067000, Hebei Province, China);Hong Zhang (Department of Surgery, Affiliated Hospital of Chengde Medical College, Chengde 067000, Hebei Province, China);Xiaohui Li (Department of Research, Affiliated Hospital of Chengde Medical College, Chengde 067000, Hebei Province, China);Bin Chen (Department of Orthopedics, Affiliated Hospital of Chengde Medical College, Chengde 067000, Hebei Province, China);
Abstract:Dark Agouti rat donor hind limbs were orthotopically transplanted into Lewis rat recipients to verify the effects of bone marrow mesenchymal stem cells on neural regeneration and functional recovery of allotransplanted limbs in the microenvironment of immunotolerance. bone marrow mesenchymal stem cells were intramuscularly (gluteus maximus) injected with FK506 (tacrolimus) daily, and were transplanted to the injured nerves. Results indicated that the allograft group not receiving therapy showed severe rejection, with transplanted limbs detaching at 10 days after transplantation with complete necrosis. The number of myelinated axons and Schwann cells in the FK506 and FK506 + bone marrow mesenchymal stem cells groups were significantly increased. We observed a lesser degree of gastrocnemius muscle degeneration, and increased polymorphic fibers along with other pathological changes in the FK506 + bone marrow mesenchymal stem cells group. The FK506 + bone marrow mesenchymal stem cells group showed significantly better recovery than the autograft and FK506 groups. The results demonstrated that FK506 improved the immune microenvironment. FK506 combined with bone marrow mesenchymal stem cells significantly promoted sciatic nerve regeneration, and improved sensory recovery and motor function in hind limb allotransplant.
Keywords:FK506 (tacrolimus)  bone marrow mesenchymal stem cells  allotransplant  hind limb transplant  function recovery  sensory function  motor function  peripheral nerve injury  regeneration  neural regeneration
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