TY - JOUR
T1 - Intravenous administration of human umbilical cord blood-derived AC133+ endothelial progenitor cells in rat stroke model reduces infarct volume
T2 - Magnetic resonance imaging and histological findings
AU - Iskander, Asm
AU - Knight, Robert A.
AU - Zhang, Zheng Gang
AU - Ewing, James R.
AU - Shankar, Adarsh
AU - Varma, Nadimpalli Ravi S.
AU - Bagher-Ebadian, Hassan
AU - Ali, Meser M.
AU - Arbab, Ali S.
AU - Janic, Branislava
PY - 2013
Y1 - 2013
N2 - 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 107 hUCB AC133EPCs. 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.
AB - 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 107 hUCB AC133EPCs. 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.
KW - Angiogenesis
KW - Brain ischemia
KW - Stem/progenitor cell
KW - Tissue regeneration
KW - Umbilical cord blood
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UR - http://www.scopus.com/inward/citedby.url?scp=84883314949&partnerID=8YFLogxK
U2 - 10.5966/sctm.2013-0066
DO - 10.5966/sctm.2013-0066
M3 - Article
C2 - 23934909
AN - SCOPUS:84883314949
SN - 2157-6564
VL - 2
SP - 703
EP - 714
JO - Stem Cells Translational Medicine
JF - Stem Cells Translational Medicine
IS - 9
ER -