Intracerebral, but not intravenous, transplantation of bone marrow stromal cells enhances functional recovery in rat cerebral infarct: an optical imaging study.
Recent studies have indicated that bone marrow stromal cells (BMSC) may improve neurological function when transplanted into an animal model of CNS disorders, including cerebral infarct. However, there are few studies that evaluate the therapeutic benefits of intracerebral and intravenous BMSC transplantation for cerebral infarct. This study was aimed to clarify the favorable route of cell delivery for cerebral infarct in rats. The rats were subjected to permanent middle cerebral artery occlusion. The BMSC were labeled with near infrared (NIR)-emitting quantum dots and were transplanted stereotactically (1 × 10⁶ cells) or intravenously (3 × 10⁶ cells) at 7 days after the insult. Using in vivo NIR fluorescence imaging technique, the behaviors of BMSC were serially visualized during 4 weeks after transplantation. Motor function was also assessed. Immunohistochemistry was performed to evaluate the fate of the engrafted BMSC. Intracerebral, but not intravenous, transplantation of BMSC significantly enhanced functional recovery. In vivo NIR fluorescence imaging could clearly visualize their migration toward the cerebral infarct during 4 weeks after transplantation in the intracerebral group, but not in the intravenous, group. The BMSC were widely distributed in the ischemic brain and some of them expressed neural cell markers in the intracerebral group, but not in the intravenous group. These findings strongly suggest that intravenous administration of BMSC has limited effectiveness at clinically relevant timing and intracerebral administration should be chosen for patients with ischemic stroke, although further studies would be warranted to establish the treatment protocol.
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Masahito
M
Kawabori
Satoshi
S
Kuroda
Taku
T
Sugiyama
Masaki
M
Ito
Hideo
H
Shichinohe
Kiyohiro
K
Houkin
Yuji
Y
Kuge
Nagara
N
Tamaki
D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology; D001854:Bone Marrow Cells / Q000648:ultrastructure; D016026:Bone Marrow Transplantation / Q000379:methods*; D001921:Brain / Q000473:pathology; D002478:Cells, Cultured; D002544:Cerebral Infarction / Q000523:psychology / Q000628:therapy*; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000628:therapy; D007275:Injections, Intravenous; D008297:Male; D009068:Movement / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010641:Phenotype; D045663:Quantum Dots; D051381:Rats; D017207:Rats, Sprague-Dawley; D019265:Spectroscopy, Near-Infrared; D013238:Stereotaxic Techniques; D017154:Stromal Cells / Q000637:transplantation*
D034961:Antigens, Nuclear; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C546339:Rbfox3 protein, rat