In vivo tracking of bone marrow stromal cells transplanted into mice cerebral infarct by fluorescence optical imaging.
Recent experimental studies have indicated that bone marrow stromal cells (BMSC) improve neurological deficits when transplanted into the animal models of various neurological disorders, although precise mechanism still remains unclear. In this study, we developed a new in vivo fluorescence optical imaging protocol to sequentially track the transplanted into the brain of the living animals subjected to cerebral infarct. Mice BMSC were harvested from transgenic mice expressing green fluorescent protein (BMSC-GFP). They were stereotactically transplanted into the ipsilateral striatum of mice subjected to permanent middle cerebral artery occlusion after 7 days of ischemia (n=12). During 12 weeks after transplantation, the skull was exposed and the green fluorescence emitted from the brain surface was sequentially observed, using in vivo fluorescence optical microscopy. As the results, regional green fluorescence was detected in the ipsilateral parietal region 4-12 weeks after transplantation in all animals and became more apparent over the time. The images obtained through the skull were very similar to those acquired by thinning or removing the skull. Immunohistochemistry evaluation revealed that the transplanted cells migrated towards the ischemic boundary zone and expressed the neuronal or astrocytic marker, supporting the findings on fluorescence optical images. Sequential visualization of the BMSC transplanted into the brain of living animals would be valuable for monitoring the migration, growth and differentiation of the transplanted cells to explore the fate and safety of stem cell transplantation for various neurological disorders.
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita, Sapporo 060-8638, Japan.
Hideo
H
Shichinohe
Satoshi
S
Kuroda
Jang-Bo
JB
Lee
Goro
G
Nishimura
Shunsuke
S
Yano
Toshitaka
T
Seki
Jun
J
Ikeda
Mamoru
M
Tamura
Yoshinobu
Y
Iwasaki
D000818:Animals; D015415:Biomarkers; D016026:Bone Marrow Transplantation / Q000295:instrumentation / Q000379:methods*; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D002544:Cerebral Infarction / Q000628:therapy*; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology / Q000601:surgery; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006085:Graft Survival / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000295:instrumentation / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D017154:Stromal Cells / Q000637:transplantation*
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins