Transplanted bone marrow stem cells relocate to infarct penumbra and co-express endogenous proliferative and immature neuronal markers in a mouse model of ischemic cerebral stroke.
BACKGROUND
Several studies demonstrate that neurogenesis may be induced or activated following vascular insults, which may be important for neuronal regeneration and functional recovery. Understanding the cellular mechanism underlying stroke-associated neurogenesis is of neurobiological as well as neurological/clinical relevance. The present study attempted to explore potential homing and early development of transplanted bone marrow stem cells in mouse forebrain after focal occlusion of the middle cerebral artery, an experimental model of ischemic stroke.


RESULTS
Bone marrow stem cells isolated from donor mice were confirmed by analysis of surface antigen profile, and were pre-labeled with a lipophilic fluorescent dye PKH26, and subsequently transfused into recipient mice with middle cerebral artery coagulation. A large number of PKH26-labeled cells were detected surrounding the infarct site, most of which colocalized with immunolabelings for the proliferating cell nuclear antigen (PCNA) and some also colocalized with the immature neuronal marker doublecortin (DCX) during 1-2 weeks after the bone marrow cells transfusion.


CONCLUSIONS
The present study shows that transplanted bone marrow cells largely relocate to the infarct penumbra in ischemic mouse cerebrum. These transplanted bone marrow cells appear to undergo a process of in situ proliferation and develop into putative cortical interneurons during the early phase of experimental vascular injury.
Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, 150086, China.
Xue-mei
XM
Zhang
Fang
F
Du
Dan
D
Yang
Chun-jiang
CJ
Yu
Xiang-nan
XN
Huang
Wei
W
Liu
Jin
J
Fu
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism*; D049109:Cell Proliferation; D002544:Cerebral Infarction / Q000628:therapy*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D009416:Nerve Regeneration / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000096:biosynthesis / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000235:genetics; D020521:Stroke / Q000378:metabolism*
C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D018809:Proliferating Cell Nuclear Antigen