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Overexpression of phosphoinositide-3-kinase class II alpha enhances mesenchymal stem cell survival in infarcted myocardium.

Authors
 Lucy Youngmin Eun  ;  Byeong-Wook Song  ;  Min-Ji Cha  ;  Heesang Song  ;  Il-Kwon Kim  ;  Eunmi Choi  ;  Woochul Chang  ;  Soyeon Lim  ;  Eun Ju Choi  ;  Onju Ham  ;  Se-Yeon Lee  ;  Ki Hyun Byun  ;  Yangsoo Jang  ;  Ki-Chul Hwang 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.402(2) : 272-279, 2010 
Journal Title
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 
ISSN
 0006-291X 
Issue Date
2010
MeSH
Animals ; Apoptosis/genetics ; Cell Survival/genetics ; Class II Phosphatidylinositol 3-Kinases/genetics* ; Genetic Engineering ; Heart/physiology* ; Male ; Mesenchymal Stem Cell Transplantation* ; Mesenchymal Stromal Cells/enzymology* ; Myocardial Infarction/enzymology ; Myocardial Infarction/pathology ; Myocardial Infarction/therapy* ; Myocardium/enzymology* ; Myocardium/pathology ; Rats ; Rats, Sprague-Dawley ; Regeneration/genetics*
Keywords
Cardiac regeneration ; Lentivirus ; Mesenchymal stem cells ; Phosphoinositide-3-kinase class II alpha ; Survival
Abstract
The efficacy of mesenchymal stem cell (MSC) therapy for myocardial regeneration is limited by the poor survival of stem cells after transplantation into the infarcted heart. To improve the cell survival of MSCs in the infarcted heart, MSCs were genetically engineered to overexpress phosphoinositide-3-kinase class II alpha (PI3K-C2α). PI3K-C2α overexpression increased PI3K expression and the cell viability of MSCs. Furthermore, levels of survival-related phosphorylation were elevated in PI3K-C2α-MSCs. But, the level of apoptotic proteins downregulated and the number of PI-positive cells decreased in PI3K-C2α-MSCs compared to hypoxic MSCs. Nine rats per group had 1×10(6) cells (20 μl PBS) transplanted after myocardial infarction. One week after transplantation, infarct size and area of fibrosis were reduced in the PI3K-C2α-MSC-transplanted group. The number of TUNEL positive cells declined, while the mean microvessel count per field was higher in the PI3K-C2α-MSC group than the MSC-injected group. Heart function was improved in the PI3K-C2α-MSCs group as assessed using a Millar catheter at 3weeks after transplantation. These findings suggest that overexpression of PI3K-C2α in MSCs can assist cell survival and enhance myocardial regeneration.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X10018644
DOI
10.1016/j.bbrc.2010.10.013
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
Yonsei Authors
Kim, Il Kwon(김일권)
Song, Byeong Wook(송병욱)
Lee, Se Yeon(이세연)
Lim, So Yeon(임소연)
Jang, Yang Soo(장양수) ORCID logo https://orcid.org/0000-0002-2169-3112
Chang, Woo Chul(장우철)
Cha, Min Ji(차민지)
Choi, Eun Mi(최은미)
Choi, Eun Ju(최은주)
Ham, On Ju(함온주)
Hwang, Ki Chul(황기철)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/102534
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