Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling

被引:553
作者
Uemura, Ryota [1 ]
Xu, Meifeng [1 ]
Ahmad, Nauman [1 ]
Ashraf, Muhammad [1 ]
机构
[1] Univ Cincinnati, Ctr Med, Dept Pathol & Lab Med, Cincinnati, OH 45267 USA
关键词
stem cells; paracrine effect; preconditioning; ischemia; remodeling;
D O I
10.1161/01.RES.0000225952.61196.39
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In this study, we hypothesized that bone marrow stem cells (BMSCs) protect ischemic myocardium through paracrine effects that can be further augmented with preconditioning. In in vitro experiments, cell survival factors such as Akt and eNOS were significantly increased in BMSCs following anoxia. In the second series of experiments following coronary ligation in mice, left ventricles were randomly injected with the following: DMEM (G-1), BMSCs (G-2), and preconditioned BMSCs (G-3). Four days after myocardial infarction, BMSCs were observed within injured myocardium in G-2 and G-3. Apoptotic cardiomyocytes within periinfarct area were significantly reduced in G-3. Four weeks after myocardial infarction, smaller left ventricular (LV) dimension and increased LV ejection fraction were observed in G-3. Infarct area was significantly reduced in G-3. However, GFP(+) cardiomyocytes were observed in low numbers within periinfarct area in G-2 and G-3. In conclusion, BMSCs secreted cell survival factors under ischemia, and they prevented apoptosis in cardiomyocytes adjacent to the infarcted area. Preconditioning of BMSCs enhanced their survival and ability to attenuate LV remodeling, which was attributable, in part, to paracrine effects.
引用
收藏
页码:1414 / 1421
页数:8
相关论文
共 40 条
[1]   Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium [J].
Balsam, LB ;
Wagers, AJ ;
Christensen, JL ;
Kofidis, T ;
Weissman, IL ;
Robbins, RC .
NATURE, 2004, 428 (6983) :668-673
[2]   Adult cardiac stem cells are multipotent and support myocardial regeneration [J].
Beltrami, AP ;
Barlucchi, L ;
Torella, D ;
Baker, M ;
Limana, F ;
Chimenti, S ;
Kasahara, H ;
Rota, M ;
Musso, E ;
Urbanek, K ;
Leri, A ;
Kajstura, J ;
Nadal-Ginard, B ;
Anversa, P .
CELL, 2003, 114 (06) :763-776
[3]   RECURRENT ISCHEMIA IN THE CANINE HEART CAUSES RECURRENT BURSTS OF FREE-RADICAL PRODUCTION THAT HAVE A CUMULATIVE EFFECT ON CONTRACTILE FUNCTION - A PATHOPHYSIOLOGICAL BASIS FOR CHRONIC MYOCARDIAL STUNNING [J].
BOLLI, R ;
ZUGHAIB, M ;
LI, XY ;
TANG, XL ;
SUN, JZ ;
TRIANA, JF ;
MCCAY, PB .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (02) :1066-1084
[4]   Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI) -: Mechanistic insights from serial contrast-enhanced magnetic resonance imaging [J].
Britten, MB ;
Abolmaali, ND ;
Assmus, B ;
Lehmann, R ;
Honold, J ;
Schmitt, J ;
Vogl, TJ ;
Martin, H ;
Schächinger, V ;
Dimmeler, S ;
Zeiher, AM .
CIRCULATION, 2003, 108 (18) :2212-2218
[5]   Transformation of chicken cells by the gene encoding the catalytic subunit of PI 3-kinase [J].
Chang, HW ;
Aoki, M ;
Fruman, D ;
Auger, KR ;
Bellacosa, A ;
Tsichlis, PN ;
Cantley, LC ;
Roberts, TM ;
Vogt, PK .
SCIENCE, 1997, 276 (5320) :1848-1850
[6]   Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction [J].
Chen, SL ;
Fang, W ;
Ye, F ;
Liu, YH ;
Qian, J ;
Shan, S ;
Zhang, J ;
Zhao, RCH ;
Liao, LM ;
Lin, S ;
Sun, JP .
AMERICAN JOURNAL OF CARDIOLOGY, 2004, 94 (01) :92-95
[7]   Molecular and cellular mechanisms of myocardial failure [J].
Colucci, WS .
AMERICAN JOURNAL OF CARDIOLOGY, 1997, 80 (11A) :L15-L25
[8]   Cellular survival: a play in three Akts [J].
Datta, SR ;
Brunet, A ;
Greenberg, ME .
GENES & DEVELOPMENT, 1999, 13 (22) :2905-2927
[9]   Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function [J].
Dawn, B ;
Stein, AB ;
Urbanek, K ;
Rota, M ;
Whang, B ;
Rastaldo, R ;
Torella, D ;
Tang, XL ;
Rezazadeh, A ;
Kajstura, J ;
Leri, A ;
Hunt, G ;
Varma, J ;
Prabhu, SD ;
Anversa, P ;
Bolli, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (10) :3766-3771
[10]   Akt takes center stage in angiogenesis signaling [J].
Dimmeler, S ;
Zeiher, AM .
CIRCULATION RESEARCH, 2000, 86 (01) :4-5