The role of stem cell factor and granulocyte-colony stimulating factor in brain repair during chronic stroke.
Chronic stroke is a highly important but under-investigated scientific problem in neurologic research. We have reported earlier that stem cell factor (SCF) in combination with granulocyte-colony stimulating factor (G-CSF) treatment during chronic stroke improves functional outcomes. Here we have determined the contribution of bone marrow-derived cells in angiogenesis and neurogenesis, which are enhanced by SCF+G-CSF treatment during chronic stroke. Using bone marrow tracking, flow cytometry, 2-photon live brain imaging, and immunohistochemistry, we observed that the levels of circulating bone marrow stem cells (BMSCs) (CD34+/c-kit+) were significantly increased by SCF+G-CSF treatment. In addition, live brain imaging revealed that numerous bone marrow-derived cells migrate into the brain parenchyma in the treated mice. We also found that bone marrow-derived cells, bone marrow-derived endothelial cells, vascular density, and bone marrow-derived neurons were significantly augmented by SCF+G-CSF. It is interesting that, in addition to the increase in bone marrow-derived endothelial cells, the number of bone marrow-derived pericytes was reduced after SCF+G-CSF treatment during chronic stroke. These data suggest that SCF+G-CSF treatment can enhance repair of brain damage during chronic stroke by mobilizing BMSCs, and promoting the contribution of bone marrow-derived cells to angiogenesis and neurogenesis.
Piao
Chun-Shu
CS
Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
Gonzalez-Toledo
Maria E
ME
Xue
Yue-Qiang
YQ
Duan
Wei-Ming
WM
Terao
Satoshi
S
Granger
D Neil
DN
Kelley
Roger E
RE
Zhao
Li-Ru
LR
D000818:Animals; D001854:Bone Marrow Cells; D001921:Brain / Q000473:pathology / Q000502:physiology*; D002560:Cerebrovascular Circulation; D002908:Chronic Disease; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology*; D051379:Mice; D018919:Neovascularization, Physiologic; D055495:Neurogenesis / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D019089:Stem Cell Factor / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology; D020521:Stroke / Q000473:pathology*
D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor