Synergistic effects of granulocyte-colony stimulating factor on bone marrow stromal cell transplantation for mice cerebral infarct.
This study was aimed to assess whether ex vivo treatment with granulocyte-colony stimulating factor (G-CSF) modifies biological properties of bone marrow stromal cells (BMSC) and enhances functional recovery by BMSC transplantation into infarct brain. Immunohistochemistry was conducted to characterize the cultured BMSC. The pharmacological effects of G-CSF on their proliferation, cell cycle, and growth factor production were precisely analyzed, using FACS and ELISA techniques. Non-treated or G-CSF treated BMSC were stereotactically transplanted into the mice brain subjected to cerebral infarct, and its effects on functional and histological aspects were evaluated. The BMSC expressed the receptor for G-CSF. Treatment with 0.1muM of G-CSF significantly enhanced the proliferation of BMSC by increasing their population in S phase, and increased their production of SDF-1alpha, HGF, and NGF. When transplanted into infarct brain, G-CSF treated BMSC significantly improved motor function as early as 2 weeks after transplantation, whereas non-treated BMSC did 4 weeks after transplantation. These findings strongly suggest that G-CSF may enhance the proliferation and growth factor production of the cultured BMSC and accelerate functional restoration by BMSC transplantation. Such pharmacological "activation" of the BMSC may contribute to successful clinical application of BMSC transplantation therapy for ischemic stroke.
Hokari
Masaaki
M
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan.
Kuroda
Satoshi
S
Chiba
Yasuhiro
Y
Maruichi
Katsuhiko
K
Iwasaki
Yoshinobu
Y
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D016026:Bone Marrow Transplantation; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002544:Cerebral Infarction / Q000628:therapy*; D054377:Chemokine CXCL12 / Q000378:metabolism; D004195:Disease Models, Animal; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D018380:Hematopoietic Stem Cell Transplantation; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D051379:Mice; D020932:Nerve Growth Factor / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D054377:Chemokine CXCL12; D016179:Granulocyte Colony-Stimulating Factor; D017228:Hepatocyte Growth Factor; D020932:Nerve Growth Factor