Therapeutic benefits by human mesenchymal stem cells (hMSCs) and Ang-1 gene-modified hMSCs after cerebral ischemia.
Transplantation of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has been reported to ameliorate functional deficits after cerebral artery occlusion in rats. Although several hypotheses to account for these therapeutic effects have been suggested, current thinking is that both neuroprotection and angiogenesis are primarily responsible. In this study, we compared the effects of hMSCs and angiopoietin-1 gene-modified hMSCs (Ang-hMSCs) intravenously infused into rats 6 h after permanent middle cerebral artery occlusion. Magnetic resonance imaging and histologic analyses revealed that rats receiving hMSCs or Ang-hMSCs exhibited comparable reduction in gross lesion volume as compared with the control group. Although both cell types indeed improved angiogenesis near the border of the ischemic lesions, neovascularization and regional cerebral blood flow were greater in some border areas in Ang-hMSC group. Both hMSC- and Ang-hMSC-treated rats showed greater improved functional recovery in the treadmill stress test than did control rats, but the Ang-hMSC group was greater. These results indicate the intravenous administration of genetically modified hMSCs to express angiopoietin has a similar effect on reducing lesion volume as hMSCs, but the Ang-hMSC group showed enhanced regions of increased angiogenesis at the lesion border, and modest additional improvement in functional outcome.
Onda
Toshiyuki
T
Department of Neurosurgery, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
Honmou
Osamu
O
Harada
Kuniaki
K
Houkin
Kiyohiro
K
Hamada
Hirofumi
H
Kocsis
Jeffery D
JD
D000256:Adenoviridae / Q000235:genetics; D042683:Angiopoietin-1 / Q000235:genetics*; D000818:Animals; D002545:Brain Ischemia / Q000628:therapy*; D004396:Coloring Agents; D005080:Exercise Test; D005697:Galactosides; D015316:Genetic Therapy; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007211:Indoles; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D013778:Tetrazolium Salts
D042683:Angiopoietin-1; D004396:Coloring Agents; D005697:Galactosides; D007211:Indoles; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside