Intravenously administered bone marrow cells migrate to damaged brain tissue and improve neural function in ischemic rats.
Accumulated evidence suggests that bone marrow stromal cells (BMSCs) are capable of regenerating damaged tissue. This study evaluated whether intravenously (noninvasively) administered, GFP-labeled BMSCs would migrate into damaged brain tissue and improve neurological function after a stroke. Wistar rats were subjected to middle cerebral artery occlusion and reperfusion. Twenty-four hours after injury, the rats received an i.v. injection of culture medium or BMSCs isolated from adult Wistar rats expressing green fluorescent protein (GFP). Two hours after injury and 1, 3, and 7 days after cell transplantation, neurological function was evaluated using a neurological severity scale. On day 7, the brain scar size was determined using tetrazolium chloride staining, and the implanted cells were identified using confocal microscopy. Immunohistochemistry was used to evaluate apoptosis and angiogenesis in the ischemic region, as well as the spatial distribution of the implanted BMSCs relative to the native neural cells. Implanted BMSCs migrated throughout the territory of the middle cerebral artery by 7 days after transplantation. Most implanted cells were located in the scar area and border zone of the ischemic region, and some expressed the neuronal marker NeuN. Rats receiving BMSC transplantation exhibited reduced scar size, limited apoptosis, and enhanced angiogenic factor expression and vascular density in the ischemic region relative to the control group, as well as significant improvements in the neurological severity scores. Intravenously administrated BMSCs facilitated the structural and functional recovery of neural tissue following ischemic injury, perhaps mediated by enhanced angiogenesis.
Wu
Jiang
J
Division of Cardiovascular Surgery, Toronto General Research Institute and University of Toronto, Toronto, Ontario, Canada.
Sun
Zhuo
Z
Sun
Hong-Shuo
HS
Wu
Jun
J
Weisel
Richard D
RD
Keating
Armand
A
Li
Zhi-Hong
ZH
Feng
Zhong-Ping
ZP
Li
Ren-Ke
RK
D000818:Animals; D017209:Apoptosis; D016026:Bone Marrow Transplantation; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D002465:Cell Movement; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007275:Injections, Intravenous; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D017154:Stromal Cells / Q000637:transplantation
D049452:Green Fluorescent Proteins