Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host

Survival and differentiation of myogenic cells grafted into infarcted myocardium have raised the hope that cell transplantation becomes a new therapy for cardiovascular diseases. The approach was further supported by transplantation of skeletal myoblasts, which was shown to improve cardiac performance in several animal species. Despite the success of myoblast transplantation and its recent trial in human, the mechanism responsible for the functional improvement remains unclear. Here, we used intracellular recordings coupled to video and fluorescence microscopy to establish whether myoblasts, genetically labeled with enhanced GFP and transplanted into rat infarcted myocardium, retain excitable and contractile properties, and participate actively to cardiac function. Our results indicate that grafted myoblasts differentiate into peculiar hyperexcitable myotubes with a contractile activity fully independent of neighboring cardiomyocytes. We conclude that mechanisms other than electromechanical coupling between grafted and host cells are involved in the improvement of cardiac function.

[1]  A. Hagège,et al.  Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. , 2003, Journal of the American College of Cardiology.

[2]  J. Saffitz,et al.  Evidence for Cardiomyocyte Repopulation by Extracardiac Progenitors in Transplanted Human Hearts , 2002, Circulation research.

[3]  K. Willecke,et al.  Quantitative analysis of gap-junctional intercellular communication in precision-cut mouse liver slices , 2002, Cell and Tissue Research.

[4]  C. Murry,et al.  Skeletal muscle stem cells do not transdifferentiate into cardiomyocytes after cardiac grafting. , 2002, Journal of molecular and cellular cardiology.

[5]  P. Anversa,et al.  Chimerism of the transplanted heart. , 2002, The New England journal of medicine.

[6]  Doris A Taylor,et al.  Cellular cardiomyoplasty with autologous skeletal myoblasts for ischemic heart disease and heart failure , 2001, Current controlled trials in cardiovascular medicine.

[7]  A. Berrebi,et al.  Cellular therapy reverses myocardial dysfunction. , 2001, The Journal of thoracic and cardiovascular surgery.

[8]  A. Hagège,et al.  Myoblast transplantation for heart failure , 2001, The Lancet.

[9]  C. Murry,et al.  Electromechanical coupling between skeletal and cardiac muscle. Implications for infarct repair. , 2000 .

[10]  D. Shum-Tim,et al.  Myocardial tissue engineering with autologous myoblast implantation. , 1998, The Journal of thoracic and cardiovascular surgery.

[11]  Doris A Taylor,et al.  Regenerating functional myocardium: Improved performance after skeletal myoblast transplantation , 1998, Nature Medicine.

[12]  C. di Loreto,et al.  Myocyte proliferation in end-stage cardiac failure in humans. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[13]  S M Schwartz,et al.  Skeletal myoblast transplantation for repair of myocardial necrosis. , 1996, The Journal of clinical investigation.

[14]  R. C. Chiu,et al.  Cellular cardiomyoplasty: myocardial regeneration with satellite cell implantation. , 1995, The Annals of thoracic surgery.

[15]  R. Kao,et al.  Myocardial regeneration. Transplanting satellite cells into damaged myocardium. , 1995, Texas Heart Institute journal.

[16]  H Korn,et al.  Electrical field effects: their relevance in central neural networks. , 1989, Physiological reviews.