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

被引：19

作者：

Eun, Lucy Youngmin ^{[2
]}

Song, Byeong-Wook ^{[1
,3
]}

Cha, Min-Ji ^{[1
,3
]}

Song, Heesang ^{[1
]}

Kim, Il-Kwon ^{[1
,3
]}

Choi, Eunmi ^{[1
,5
]}

Chang, Woochul ^{[1
]}

Lim, Soyeon ^{[1
]}

Choi, Eun Ju ^{[1
,3
]}

Ham, Onju ^{[1
,3
]}

Lee, Se-Yeon ^{[1
,3
]}

Byun, Ki Hyun ^{[2
]}

Jang, Yangsoo ^{[1
,3
,4
]}

Hwang, Ki-Chul ^{[1
,3
,5
]}

机构：

[1] Yonsei Univ, Coll Med, Cardiovasc Res Inst, Seoul 120752, South Korea

[2] Kwandong Univ Coll Med, Myongji Hosp Cardiac Ctr, Dept Pediat, Div Pediat Cardiol, Seoul, South Korea

[3] Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21, Seoul 120752, South Korea

[4] Yonsei Univ, Coll Med, Div Cardiol, Seoul 120752, South Korea

[5] Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul 120752, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2010年 / 402卷 / 02期

关键词：

Cardiac regeneration; Lentivirus; Mesenchymal stem cells; Phosphoinositide-3-kinase class II alpha; Survival; IMPROVES CARDIAC-FUNCTION; ISCHEMIC-MYOCARDIUM; REPAIR; DEATH; TRANSPLANTATION; 3-KINASE; GROWTH; HEART; EXPRESSION; STRATEGIES;

D O I：

10.1016/j.bbrc.2010.10.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-C2 alpha). PI3K-C2 alpha overexpression increased PI3K expression and the cell viability of MSCs. Furthermore, levels of survival-related phosphorylation were elevated in PI3K-C2 alpha-MSC5. But, the level of apoptotic proteins downregulated and the number of PI-positive cells decreased in PI3K-C2a-MSC5 compared to hypoxic MSCs. Nine rats per group had 1 x 10(6) cells (20 mu I PBS) transplanted after myocardial infarction. One week after transplantation, infarct size and area of fibrosis were reduced in the PI3K-C2 alpha-MSC-transplanted group. The number of TUNEL positive cells declined, while the mean microvessel count per field was higher in the PI3K-C2 alpha-MSC group than the MSC-injected group. Heart function was improved in the PI3K-C2 alpha-MSC5 group as assessed using a Millar catheter at 3 weeks after transplantation. These findings suggest that overexpression of PI3K-C2a in MSCs can assist cell survival and enhance myocardial regeneration. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：272 / 279

页数：8

共 31 条

[1]

Amado LC, 2005, P NATL ACAD SCI USA, V102, P11474, DOI 10.1073/pnas.0504388102

[2] Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium - Feasibility, cell migration, and body distribution [J].

Barbash, IM ;

Chouraqui, P ;

Baron, J ;

Feinberg, MS ;

Etzion, S ;

Tessone, A ;

Miller, L ;

Guetta, E ;

Zipori, D ;

Kedes, LH ;

Kloner, RA ;

Leor, J .

CIRCULATION, 2003, 108 (07) :863-868

[3] Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance [J].

Berry, Mark F. ;

Engler, Adam J. ;

Woo, Y. Joseph ;

Pirolli, Timothy J. ;

Bish, Lawrence T. ;

Jayasankar, Vasant ;

Morine, Kevin J. ;

Gardner, Timothy J. ;

Discher, Dennis E. ;

Sweeney, H. Lee .

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2006, 290 (06) :H2196-H2203

[4] Stem cells and their potential in cell-based cardiac therapies [J].

Christoforou, Nicolas ;

Gearhart, John D. .

PROGRESS IN CARDIOVASCULAR DISEASES, 2007, 49 (06) :396-413

[5] Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery [J].

Datta, SR ;

Dudek, H ;

Tao, X ;

Masters, S ;

Fu, HA ;

Gotoh, Y ;

Greenberg, ME .

CELL, 1997, 91 (02) :231-241

[6] Overexpressing cellular repressor of E1A-stimulated genes protects mesenchymal stem cells against hypoxia- and serum deprivation-induced apoptosis by activation of PI3K/Akt [J].

Deng, Jie ;

Han, Yaling ;

Yan, Chenhui ;

Tian, XIaoxiang ;

Tao, Jie ;

Kang, Jian ;

Li, Shaohua .

APOPTOSIS, 2010, 15 (04) :463-473

[7] Down-regulation of class II phosphoinositide 3-kinase α expression below a critical threshold induces apoptotic cell death [J].

Elis, Winfried ;

Triantafellow, Ellen ;

Wolters, Natalie M. ;

Sian, Katie R. ;

Caponigro, Giordano ;

Borawski, Jason ;

Gaither, L. Alex ;

Murphy, Leon O. ;

Finan, Peter M. ;

MacKeigan, Jeffrey P. .

MOLECULAR CANCER RESEARCH, 2008, 6 (04) :614-623

[8] The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism [J].

Engelman, Jeffrey A. ;

Luo, Ji ;

Cantley, Lewis C. .

NATURE REVIEWS GENETICS, 2006, 7 (08) :606-619

[9] The immune system and cardiac repair [J].

Frangogiannis, Nikolaos G. .

PHARMACOLOGICAL RESEARCH, 2008, 58 (02) :88-111

[10] BCL-2 family members and the mitochondria in apoptosis [J].

Gross, A ;

McDonnell, JM ;

Korsmeyer, SJ .

GENES & DEVELOPMENT, 1999, 13 (15) :1899-1911

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