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2005 Fiscal Year Final Research Report Summary

Study of transplantation of endothelial progenitor cells in rat cerebral infarction model to minimize the infarction size for the clinical application in the future

Research Project

Project/Area Number 16591814
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Emergency medicine
Research InstitutionWakayama Medical University

Principal Investigator

UENO Masami  Wakayama Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (10309544)

Co-Investigator(Kenkyū-buntansha) KAWASAKI Sadao  Wakayama Medical University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (50254553)
TAKAESU Hideki  Wakayama Medical University, Faculty of Medicine, Assistant, 医学部, 助手 (60347581)
SHINOZAKI Maki  Wakayama Medical University, Faculty of Medicine, Assistant, 医学部, 助手 (00326381)
Project Period (FY) 2004 – 2005
Keywordsendothelial progenitor cell / cerebral infarction / transplantation
Research Abstract

In 2004, we found that the number of peripheral endothelial progenitor cells (EPCs) with CD34(+)/CD133(+) increased three times significantly 14 days after cerebral infarction using a Sprague-Dawley (SD) rat ischemic model and contributed directly to neovascularization in the infracted area, suggesting the possibility that EPCs might affect the pathological course of brain ischemia.
Based on these basic results, we sought to evaluate the effect of EPC-transplantation on cerebral infarction histopathologically. First, we purified EPCs from peripheral blood of the rats with cerebral infarction operated by a Koizumi method and cultured to propagate the cells in vitro. We also prepared another series of rats with cerebral infarction for the EPC-transplantation by the same metod. Just after generating the infarction, the cultured EPCs or PBS (control) were injected into the infracted area of the rats brain and those was sacrificed after 7 and 14 days followed by histopathological evaluation … More of the brain tissue. At day 7, no difference of the infarted size was found between EPCs transplanted (n=12) and control rats (n=10). However, at day 14, the size was found to be smaller significantly in transplanted rats (n=12) than controls (n=12). Furthermore, the matured BS-1 lectin positive endothelial cells labeled with Dil-acetyl LDL at day 14 were incorporated in the reconstituted neovasculature and these findings were evident especially around the core of infarction, so called, ischemic penumbra.
These results together suggested the possibility that bone marrow derived-EPCs participated in neovascularization in the cerebral infarction and had an important roles to protect the ischemic penumbra, at least in part, through enrichment of blood supply by promoting neovascularization. We are now studing whether EPC-transplanted rats will behave their physiological improvement and optimamization of the metod, the cell-number, and the timing of EPC-transplantation for clinical application in the near future. Less

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Published: 2007-12-13  

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