Noninvasive transplantation of bone marrow stromal cells for ischemic stroke: preliminary study with a thermoreversible gelation polymer hydrogel.
OBJECTIVE
Recent studies have indicated that bone marrow stromal cells (BMSCs) have the potential to improve neurological function when transplanted into animal models of cerebral infarct. However, it is still undetermined how the BMSCs should be transplanted to obtain the most efficient therapeutic benefits safely. The aim of this study was to assess whether a thermoreversible gelation polymer (TGP) hydrogel acts as a noninvasive, valuable scaffold in BMSC transplantation for infarct brain.


METHODS
The mice were subjected to permanent middle cerebral artery occlusion. Vehicle, BMSC suspension, or the BMSC-TGP construct was transplanted onto the ipsilateral intact neocortex at 7 days after the insult. Neurological symptoms were assessed throughout the experiments. The fate of the transplanted BMSC was examined 8 weeks after transplantation with immunohistochemistry.


RESULTS
TGP hydrogel completely disappeared and provoked no inflammation in the host brain. Many transplanted cells were widely engrafted in the ipsilateral cerebrum, including the dorsal neocortex adjacent to the cerebral infarct in the BMSC-TGP construct-treated mice. Their number was significantly larger than in the BMSC-treated mice. The majority were positive for both NeuN and MAP2 and morphologically simulated the neurons.


CONCLUSIONS
The findings suggest that surgical transplantation of tissue-engineered BMSCs onto the intact neocortex enhances the engraftment of donor cells around the cerebral infarct. These data may be useful in developing a noninvasive but efficient paradigm in neural tissue engineering. TGP hydrogel can be a promising candidate for valuable scaffolds in BMSC transplantation for central nervous system disorders because of its unique biochemical properties.
Osanai
Toshiya
T
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Kuroda
Satoshi
S
Yasuda
Hiroshi
H
Chiba
Yasuhiro
Y
Maruichi
Katsuhiko
K
Hokari
Masaaki
M
Sugiyama
Taku
T
Shichinohe
Hideo
H
Iwasaki
Yoshinobu
Y
D000818:Animals; D001704:Biopolymers / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000379:methods*; D002478:Cells, Cultured; D002544:Cerebral Infarction / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D020100:Hydrogels / Q000627:therapeutic use*; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000628:therapy; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017154:Stromal Cells / Q000187:drug effects / Q000637:transplantation; D054457:Tissue Scaffolds; D016896:Treatment Outcome
D001704:Biopolymers; D020100:Hydrogels