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Mesenchymal stem cells for ischemic stroke: changes in effects after ex vivo culturing

Authors
 Wen Yu Li  ;  Yun Jung Choi  ;  Phil Hyu Lee  ;  Kyoon Huh  ;  Yoon Mi Kang  ;  Hyun Soo Kim  ;  Young Hwan Ahn  ;  Gwang Lee  ;  Oh Young Bang 
Citation
 CELL TRANSPLANTATION, Vol.17(9) : 1045-1059, 2008 
Journal Title
CELL TRANSPLANTATION
ISSN
 0963-6897 
Issue Date
2008
MeSH
Animals ; Behavior, Animal ; Brain Infarction/pathology ; Brain Infarction/therapy* ; Cells, Cultured ; Male ; Mesenchymal Stem Cell Transplantation* ; Mesenchymal Stem Cells/cytology* ; Neurogenesis ; Neuroglia/pathology ; Neurons/pathology* ; Rats ; Rats, Sprague-Dawley
Keywords
Animals ; Behavior, Animal ; Brain Infarction/pathology ; Brain Infarction/therapy* ; Cells, Cultured ; Male ; Mesenchymal Stem Cell Transplantation* ; Mesenchymal Stem Cells/cytology* ; Neurogenesis ; Neuroglia/pathology ; Neurons/pathology* ; Rats ; Rats, Sprague-Dawley
Abstract
Although ex vivo culture expansion is necessary to use autologous mesenchymal stem cells (MSCs) in treating stroke patients, and several researchers have utilized culture-expanded cells in their studies, the effects of culture expansion on neurogenesis and trophic support are unknown. Thus, we evaluated the impact of the passage of MSCs on their effects in a rat stroke model. The i.v. application of ex vivo-cultured human MSCs, earlier (passage 2) or later passage (passage 6), was performed in a rat stroke model. Behavioral tests, immunohistochemical studies, and quantitative analysis using the CAST-grid system were performed to evaluate the degree of neurogenesis. We also evaluated the levels of trophic factors in both control and MSC-treated rat brain extract. Compared to rats that received later-passage human MSCs, behavioral recovery and neurogenesis as revealed by bromodeoxyuridine staining were more pronounced in rats that received earlier-passage human MSCs (p < 0.01 in both cases). Double staining showed that most of the endogenous neuronal progenitor cells, but few human MSCs, expressed neuronal and glial phenotypes. Tissue levels of trophic factors, including glial cell line-derived neurotrophic factor, nerve growth factor, vascular endothelial growth factor, and hepatocyte growth factor, were higher in earlier-passage MSC-treated brains than in control or later-passage MSC-treated brains (p < 0.01 in all cases). Our results indicate that ischemia-induced neurogenesis was enhanced by the i.v. administration of human MSCs. The effects were more pronounced with earlier-passage than with later-passage human MSCs, which may be related to the differential capacity in trophic support, depending on their passage.
Full Text
http://www.ingentaconnect.com/content/cog/ct/2008/00000017/00000009/art00006
DOI
19177841
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108082
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