Fate of undifferentiated mouse embryonic stem cells within the rat heart: role of myocardial infarction and immune suppression

被引:24
作者
He, Qing [2 ]
Trindade, Pedro T. [3 ]
Stumm, Michael [6 ]
Li, Jian [2 ]
Zammaretti, Prisca [7 ,8 ]
Bettiol, Esther [2 ]
Dubois-Dauphin, Michel [2 ]
Herrmann, Francois
Kalangos, Afksendyios [5 ]
Morel, Denis [4 ]
Jaconi, Marisa E. [1 ,2 ]
机构
[1] Univ Geneva, Fac Med, Dept Pathol & Immunol, CH-1211 Geneva, Switzerland
[2] Univ Hosp Geneva, Dept Rehabil & Geriatr, Lab Biol Aging, Geneva, Switzerland
[3] Univ Hosp Geneva, Div Cardiol, Geneva, Switzerland
[4] Univ Hosp Geneva, Dept Invest Anesthesiol, Geneva, Switzerland
[5] Univ Hosp Geneva, Serv Cardiovasc Surg, Geneva, Switzerland
[6] Univ Basel Hosp, Dept Res, Basel, Switzerland
[7] Ecole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland
[8] Ecole Polytech Fed Lausanne, Inst Chem Sci & Engn, CH-1015 Lausanne, Switzerland
基金
瑞士国家科学基金会;
关键词
mouse embryonic stem cells; cell therapy; myocardial infarction; immunosuppression; rat; CYCLOSPORINE-A; TRANSPLANTATION; EXPRESSION; DIFFERENTIATION; AUTOFLUORESCENCE; IMPROVEMENT; ENGRAFTMENT; INDUCTION; TERATOMAS; PROTEINS;
D O I
10.1111/j.1582-4934.2008.00323.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
It has recently been suggested that the infarcted rat heart microenvironment could direct pluripotent mouse embryonic stem cells to differentiate into cardiomyocytes through an in situ paracrine action. To investigate whether the heart can function as a cardiogenic niche and confer an immune privilege to embryonic stem cells, we assessed the cardiac differentiation potential of undifferentiated mouse embryonic stem cells (mESC) injected into normal, acutely or chronically infarcted rat hearts. We found that mESC survival depended on immunosuppression both in normal and infarcted hearts. However, upon Cyclosporin A treatment, both normal and infarcted rat hearts failed to induce selective cardiac differentiation of implanted mESC. Instead, teratomas developed in normal and infarcted rat hearts 1 week and 4 weeks (50% and 100%, respectively) after cell injection. Tight control of ESC commitment into a specific cardiac lineage is mandatory to avoid the risk of uncontrolled growth and tumourigenesis following transplantation of highly plastic cells into a diseased myocardium.
引用
收藏
页码:188 / 201
页数:14
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