Optimization of a therapeutic protocol for intravenous injection of human mesenchymal stem cells after cerebral ischemia in adult rats.
The systemic injection of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has therapeutic benefits after cerebral artery occlusion in rats, and may have multiple therapeutic effects at various sites and times within the lesion as the cells respond to a particular pathological microenvironment. However, the comparative therapeutic benefits of multiple injections of hMSCs at different time points after cerebral artery occlusion in rats remain unclear. In this study, we induced middle cerebral artery occlusion (MCAO) in rats using intra-luminal vascular occlusion, and infused hMSCs intravenously at a single 6 h time point (low and high cell doses) and various multiple time points after MCAO. From MRI analyses lesion volume was reduced in all hMSC cell injection groups as compared to serum alone injections. However, the greatest therapeutic benefit was achieved following a single high cell dose injection at 6 h post-MCAO, rather than multiple lower cell infusions over multiple time points. Three-dimensional analysis of capillary vessels in the lesion indicated that the capillary volume was equally increased in all of the cell-injected groups. Thus, differences in functional outcome in the hMSC transplantation subgroups are not likely the result of differences in angiogenesis, but rather from differences in neuroprotective effects.
Omori
Yoshinori
Y
Department of Neurosurgery, Sapporo Medical University School of Medicine, Sapporo, Hokkaido 060-8543, Japan.
Honmou
Osamu
O
Harada
Kuniaki
K
Suzuki
Junpei
J
Houkin
Kiyohiro
K
Kocsis
Jeffery D
JD
D000704:Analysis of Variance; D000818:Animals; D020520:Brain Infarction / Q000473:pathology / Q000517:prevention & control; D002545:Brain Ischemia / Q000473:pathology / Q000601:surgery*; D002196:Capillaries / Q000473:pathology; D002985:Clinical Protocols; D004195:Disease Models, Animal; D005260:Female; D005697:Galactosides / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000378:metabolism; D007275:Injections, Intravenous / Q000379:methods; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts; D013997:Time Factors; D014183:Transplantation, Heterologous
D005697:Galactosides; D007211:Indoles; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside