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Transplantation of human bone marrow stromal cell‐derived Schwann cells reduces cystic cavity and promotes functional recovery after contusion injury of adult rat spinal cord
Authors:Takahito Kamada  Masao Koda  Mari Dezawa  Reiko Anahara  Yoshiro Toyama  Katsunori Yoshinaga  Masayuki Hashimoto  Shuhei Koshizuka  Yutaka Nishio  Chikato Mannoji  Akihiko Okawa  Masashi Yamazaki
Affiliation:1. Departments of Orthopaedic Surgery,;2. Department of Orthopaedic Surgery, Chiba Aoba Municipal Hospital, Chiba;3. Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, and;4. Bioenvironmental Medicine and;5. Anatomy and Developmental Biology, Chiba University Graduate School of Medicine, Chiba,;6. Chiba Rehabilitation Center, Chiba, Japan
Abstract:
The aim of this study was to evaluate whether transplantation of human bone marrow stromal cell‐derived Schwann cells (hBMSC‐SC) promotes functional recovery after contusive spinal cord injury of adult rats. Human bone marrow stromal cells (hBMSC) were cultured from bone marrow of adult human patients and induced into Schwann cells (hBMSC‐SC) in vitro. Schwann cell phenotype was confirmed by immunocytochemistry. Growth factors secreted from hBMSC‐SC were detected using cytokine antibody array. Immunosppressed rats were laminectomized and their spinal cords were contused using NYU impactor (10 g, 25 mm). Nine days after injury, a mixture of Matrigel and hBMSC‐SC (hBMSC‐SC group) was injected into the lesioned site. Five weeks after transplantation, cresyl‐violet staining revealed that the area of cystic cavity was smaller in the hBMSC‐SC group than that in the control group. Immunohistochemstry revealed that the number of anti‐growth‐associated protein‐43‐positive nerve fibers was significantly larger in the hBMSC‐SC group than that in the control group. At the same time, the number of tyrosine hydroxylase‐ or serotonin‐positive fibers was significantly larger at the lesion epicenter and caudal level in the hBMSC‐SC group than that in the control group. In electron microscopy, formation of peripheral‐type myelin was recognized near the lesion epicenter in the hBMSC‐SC group. Hind limb function recovered significantly in the hBMSC‐SC group compared with the control group. In conclusion, the functions of hBMSC‐SC are comparable to original Schwann cells in rat spinal cord injury models, and are thus potentially useful treatments for patients with spinal cord injury.
Keywords:axonal regeneration  bone marrow stromal cell  hind limb function  Schwann cell  spinal cord injury
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