Stem cells to regenerate the heart (august 21st, 2007)

The Inserm AVENIR team headed by Michel Pucéat (Inserm Unit 861: I-STEM) is one of the first French teams allowed to work with human embryonic stem cells in France. In collaboration with Philippe Menasché, a cardiac Surgeon at the Georges Pompidou European Hospital (AP-HP, Paris 5 University) and Director of the INSERM Unit 633 “Cell therapy in cardiovascular diseases”, Michel Pucéat’s team has demonstrated for the first time that human embryonic stem cells can differentiate into cardiac cells in rat infarcted hearts. This work was performed in the laboratory of I-Stem, headed by Marc Peschanski, in co-ordination with a partnership between the French Association against Myopathy (AFM), Inserm, Genopole and the University of Evry, and was published in the Journal Stem Cells.

Being one of the first teams in France which has been allowed to work on this type of cell, the team of Michel Pucéat at Inserm Unit 861 (I-stem) has published the first french study on human embryonic stem cells, in the journal “Stem Cells”. This publication is the result of a close collaboration between Michel Pucéat’s team and Inserm Unit 633 headed by Philippe Menasché. The scientists have focused on embryonic stem cells to regenerate damaged heart tissue in cardiac contractility failures. This disorder, which has a multifactorial origin (infarction, heart disease or genetic muscular dystrophy…) is a major cause of death in most developed countries, including France. In heart failure, part of the heart muscle (myocardium) is damaged and the tissue is replaced by fibrotic and non-contractile tissue. Myocardium therefore loses its elasticity, does not contract properly anymore and can no longer fulfil its function. For patients suffering from heart failure, pharmacology remains rather limited. Given the lack of capacity for heart regeneration and paucity of donors for heart transplants, the use of human embryonic stem cells is an excellent approach to restore a failing myocardium.

 The hope of embryonic stem cells

Many experiments have been or are currently performed with adult stem cells (myoblasts, hematopoietic stem cells, or mesenchymal), but their differentiation into heart cells (cardiomyocytes) has not been proven so far. In contrast, studies on animals have shown that animal embryonic stem cells can differentiate into cardiac cells and regenerate damaged tissues. The team of Michel Pucéat had therefore tried this experiment with human embryonic stem cells.

To this end, they exposed human embryonic stem cells to a growth factor (BMP2), priming them for a possible differentiation. Then, “engaged” stem cells were implanted into damaged heart tissues of immunosuppressed rats, victims of a heart attack. Two months later, the researchers found that human heart cells had developed within the damaged area. In this environment, “oriented” stem cells have differentiated into cardiomyocytes and cardiac tissue began to recover. In addition, the researchers did not detect any tumors (teratoma), inflammation, or undesirable side effects which are common after this type of transplantation. Although additional biological studies are still needed to improve the tested protocol and secure cell’s differentiation, ie prevent the cardiomyocytes not to become undifferentiated cells, these promising results open up the use of embryonic stem cells in the treatment of cardiac deficiencies, whatever their origin.

 

 

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