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.
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. Immunosuppressed 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. Immunohistochemistry 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.
Kamada
Takahito
T
Department of Orthopaedic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
Koda
Masao
M
Dezawa
Mari
M
Anahara
Reiko
R
Toyama
Yoshiro
Y
Yoshinaga
Katsunori
K
Hashimoto
Masayuki
M
Koshizuka
Shuhei
S
Nishio
Yutaka
Y
Mannoji
Chikato
C
Okawa
Akihiko
A
Yamazaki
Masashi
M
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D003560:Cysts / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D009416:Nerve Regeneration / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D012583:Schwann Cells / Q000378:metabolism / Q000637:transplantation* / Q000648:ultrastructure; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D055815:Young Adult