Intravenous administration of human umbilical cord blood-derived AC133+ endothelial progenitor cells in rat stroke model reduces infarct volume: magnetic resonance imaging and histological findings.
Endothelial progenitor cells (EPCs) hold enormous therapeutic potential for ischemic vascular diseases. Previous studies have indicated that stem/progenitor cells derived from human umbilical cord blood (hUCB) improve functional recovery in stroke models. Here, we examined the effect of hUCB AC133+ EPCs on stroke development and resolution in a middle cerebral artery occlusion (MCAo) rat model. Since the success of cell therapies strongly depends on the ability to monitor in vivo the migration of transplanted cells, we also assessed the capacity of magnetic resonance imaging (MRI) to track in vivo the magnetically labeled cells that were administered. Animals were subjected to transient MCAo and 24 hours later injected intravenously with 10(7) hUCB AC133+ EPCs. MRI performed at days 1, 7, and 14 after the insult showed accumulation of transplanted cells in stroke-affected hemispheres and revealed that stroke volume decreased at a significantly higher rate in cell-treated animals. Immunohistochemistry analysis of brain tissues localized the administered cells in the stroke-affected hemispheres only and indicated that these cells may have significantly affected the magnitude of endogenous proliferation, angiogenesis, and neurogenesis. We conclude that transplanted cells selectively migrated to the ischemic brain parenchyma, where they exerted a therapeutic effect on the extent of tissue damage, regeneration, and time course of stroke resolution.
Department of Radiology, Henry Ford Hospital, Detroit, MI, USA.
Asm
A
Iskander
Robert A
RA
Knight
Zheng Gang
ZG
Zhang
James R
JR
Ewing
Adarsh
A
Shankar
Nadimpalli Ravi S
NR
Varma
Hassan
H
Bagher-Ebadian
Meser M
MM
Ali
Ali S
AS
Arbab
Branislava
B
Janic
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D036101:Cord Blood Stem Cell Transplantation; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D010455:Peptides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D020521:Stroke / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D014183:Transplantation, Heterologous
D000071916:AC133 Antigen; D015703:Antigens, CD; D015415:Biomarkers; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides
Angiogenesis; Brain ischemia; Stem/progenitor cell; Tissue regeneration; Umbilical cord blood