This project has many originalities :

• Discovery of rare isl1+ cardiac progenitors and defined systems for their renewal and differentiation in vitro and in vivo

• Pioneering state of the art concepts and technologies for cell transplantation therapy for human heart failure

• Cooperation between teams with very strong expertise in i) cell biology of cardiac and muscle growth and differentiation, ii) molecular genetics and functional genomics of cardiomyopathies, iii) heart tissue engineering, iv) clinical aspects of heart diseases and v) translational medicine and surgery

• Strong History of Trans-Atlantic Network Collaboration : over the past two decades, Drs. Schwartz and Chien have a strong history of collaboration between their groups. A strong cohesive, collaborative research track record also exists within each European and US networks

• Outstanding track record of network leaders and investigators in translational medicine: as the first application of cell-based, regenerative medicine to human heart disease, the study of Drs. Menasché and Schwartz has set a standard for how cell-based therapies can be moved safely to the clinic. Dr. Schwartz has been a leader in the genetics of human cardiomyopathies for over two decades. Dr. Chien has developed several new therapeutic strategies for heart failure that are currently in development for clinical studies, and has effectively combined work in both experimental and human studies.

• Integration of internationally leading expertise in cardiovascular science, medicine, surgery, commercial GMP manufacturing, and clinical trial regulatory issues. 

Oct4 nuclear staining of HuES cells

Hoechst nuclear staining of HuES cells

Thus the objectives of the network are:

1) To isolate, characterize, and generate the cardioblast renewal factor from cardiac mesenchymal cells (CBRF)

2) To identify, purify, renew, and differentiate human derived isl1+ cardioblasts into functional cardiac myocytes in vitro and in vivo

3) To identify the role of endogenous isl1+ cardioblasts in in vivo cardiac repair, regeneration, and to explore in vitro and in vivo their use for cardiac tissue engineering in the presence and absence of exogenous CBRF

4) To establish the role of isl1+ cardioblasts and related pathways in cardiac diseases (congenital heart disease, arrhythmogenesis, cardiomyopathy, and heart failure) and closely related forms of neuromuscular disease

5) To establish the experimental and clinical conditions for in vivo cardiac repair with expanded cultures of autologous isl1+ cardioblasts in the failing heart

6) To test the possible involvement of the genes responsible for cardioblast differentiation in the development of human cardiomyopathies