Transplantation of embryonic stem cells into the infarcted mouse heart: formation of multiple cell types

被引:105
作者
Singla, DK
Hacker, TA
Ma, LN
Douglas, PS
Sullivan, R
Lyons, GE
Kamp, TJ
机构
[1] Univ Wisconsin, Dept Med, Madison, WI 53792 USA
[2] Univ Wisconsin, WiCell Res Inst, Madison, WI 53792 USA
[3] Univ Wisconsin, Waisman Ctr, Madison, WI 53792 USA
[4] Univ Wisconsin, Dept Anat, Madison, WI 53792 USA
关键词
embryonic stem cells; myocardial infarction; regeneration; cardiomyocytes; cell therapy;
D O I
10.1016/j.yjmcc.2005.09.001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Initial Studies have suggested that transplantation of embryonic stem (ES) cells following myocardial infarction (MI) in animal models is beneficial; however, the mechanism of benefit is largely unknown. The present study investigated the fate of mouse ES cells transplanted post-MI to determine if the ES cells give rise to the range of major cell types present in the native myocardium. MI was produced by coronary artery ligation in C57BL/6 mice. Two different mouse ES cell lines, expressing eGFP and beta-galactosidase, respectively, were tested. Post-MI intramyocardial injection of 3 x 10(4) ES cells was compared to injection of media alone. Histochemistry and immunofluorescence were used to track the transplanted ES cells and identify the resulting cell types. Echocardiography assessed the cardiac size and function in a blinded fashion. Two weeks post-MI, engraftment of the transplanted ES cells was demonstrated by eGFP or beta-galactosidase-positive cells in the infarct region without evidence for tumor formation. Co-immunolabeling demonstrated that the transplanted ES cells had become cardiomyocytes, vascular smooth muscle, and endothelial cells. Echocardiographic analysis showed that ES cell transplantation resulted in reduced post-MI remodeling of the heart and improved cardiac function. In conclusion, transplanted mouse ES cells can regenerate infarcted myocardium in part by becoming cardiomyocytes, vascular smooth muscle, and endothelial cells that result in an improvement in cardiac structure and function. Therefore, ES cells hold promise for myocardial cellular therapy. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:195 / 200
页数:6
相关论文
共 12 条
[1]   In vitro preselection of gene-trapped embryonic stem cell clones for characterizing novel developmentally regulated genes in the mouse [J].
Baker, RK ;
Haendel, MA ;
Swanson, BJ ;
Shambaugh, JC ;
Micales, BK ;
Lyons, GE .
DEVELOPMENTAL BIOLOGY, 1997, 185 (02) :201-214
[2]   Stem cell differentiation requires a paracrine pathway in the heart [J].
Behfar, A ;
Zingman, LV ;
Hodgson, DM ;
Rauzier, JM ;
Kane, GC ;
Terzic, A ;
Pucéat, M .
FASEB JOURNAL, 2002, 16 (12) :1558-1566
[3]   Differentiation of pluripotent embryonic stem cells into cardiomyocytes [J].
Boheler, KR ;
Czyz, J ;
Tweedie, D ;
Yang, HT ;
Anisimov, SV ;
Wobus, AM .
CIRCULATION RESEARCH, 2002, 91 (03) :189-201
[4]   Stable benefit of embryonic stem cell therapy in myocardial infarction [J].
Hodgson, DM ;
Behfar, A ;
Zingman, LV ;
Kane, GC ;
Perez-Terzic, C ;
Alekseev, AE ;
Pucéat, M ;
Terzic, A .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2004, 287 (02) :H471-H479
[5]   Transforming growth factor-β2 enhances differentiation of cardiac myocytes from embryonic stem cells [J].
Kumar, D ;
Sun, BM .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 332 (01) :135-141
[6]   Distinct mouse coronary anatomy and myocardial infarction consequent to ligation [J].
Kumar, D ;
Hacker, TA ;
Buck, J ;
Whitesell, LF ;
Kaji, EH ;
Douglas, PS ;
Kamp, TJ .
CORONARY ARTERY DISEASE, 2005, 16 (01) :41-44
[7]   Stem-cell transplantation in myocardial infarction: A status report [J].
Lee, MS ;
Makkar, RR .
ANNALS OF INTERNAL MEDICINE, 2004, 140 (09) :729-737
[8]   Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts [J].
Mangi, AA ;
Noiseux, N ;
Kong, DL ;
He, HM ;
Rezvani, M ;
Ingwall, JS ;
Dzau, VJ .
NATURE MEDICINE, 2003, 9 (09) :1195-1201
[9]   Molecular and cell-based therapies for protection, rescue, and repair of ischemic myocardium - Reasons for cautious optimism [J].
Melo, LG ;
Pachori, AS ;
Kong, D ;
Gnecchi, M ;
Wang, K ;
Pratt, RE ;
Dzau, VJ .
CIRCULATION, 2004, 109 (20) :2386-2393
[10]   Transplantation of embryonic stem cells improves cardiac function in postinfarcted rats [J].
Min, JY ;
Yang, YK ;
Converso, KL ;
Liu, LX ;
Huang, Q ;
Morgan, JP ;
Xiao, YF .
JOURNAL OF APPLIED PHYSIOLOGY, 2002, 92 (01) :288-296