Stem Cells, Cardiovascular pathophysiology and Biothérapies

Cardiovascular diseases are the leading cause of morbidity and mortality in industrialized countries and its incidence are increasing steadily due to the progressive ageing of the population. The main theme of our research team is firmly in this major public health issue. 

Our main objective is to determine the molecular and pathophysiological mechanisms involved in the development of cardiovascular diseases in order to develop new therapeutic strategies for these diseases. 

We address these issues through research on stem cells and the development of bio-inspired biomaterials. 

Using multidisciplinary approaches our goals are:

  • to obtain cardiac progenitors capable of proliferating and differentiating into real ventricular cardiomyocytes from human pluripotent stem cells; 
  • to develop bio-inspired biomaterials for cardiac engineering mimicking the fibrous structure and the mechanical properties of the myocardium; 
  • to elaborate the behavior of these cardiac progenitors in response to various physiological and pathological stimuli;
  • to evaluate the therapeutic potential of cellularized biomaterials.

More...

The use of stem cells and biomaterials has become crucial in the field of cardiovascular research both for the development of new therapeutic approaches and for the creation of new cellular models to study cardiovascular diseases and ageing. Biomaterials are used to create a bio-inspired environment that mimics the morphology and properties of the extracellular matrix of the tissue of interest.

The aim of our team is to develop biomaterials for cardiac engineering mimicking the alveolar and fibrous structure and the mechanical properties of the myocardium. In this context, we first developped different biomaterials composed of nanofibers from extracellular matrix components (i.e. collagen). In a second step, these biocompatible and biodegradable biomaterials are seeded with cardiovascular progenitors derived from human pluripotent stem cells. The creation of these cellularized biomaterials allows us to create a cellular model for studying the behavior of these cardiac progenitors in response to various physiological and pathological stimuli and also to develop new medical devices for cardiovascular diseases.

Indeed, cardiac cell therapy holds a real promise for improving function of the chronically failing myocardium. However, so far, clinical outcomes of patients included in cell therapy trials have not met the expectations raised by the preceding experimental studies. Analysis of the causes for these suboptimal results leads to three major conclusions :

  • repair of scarred myocardium could be more efficient by the use of cells endowed with a higher cardiomyogenic differentiation potential as compared to cell types used so far clinically (skeletal myoblasts, bone marrow-derived cells, adipose tissue-derived cells) that lack the ability to convert into cardiomyocytes;
  • injection-based cell delivery is not satisfactory, primarily because it involves a proteolytic dissociation of the cells which sets the stage for their apoptotic death;
  • the efficacy of the cell transplant is largely dependent on the engraftment rate which, in turn, requires cells to receive an adequate blood supply to survive.

To address these issues, since 2009, we switched from mere cell therapy to a more composite tissue engineering approach entailing the use of human pluripotent stem cell (hESC)-derived cardiovascular progenitors and biocompatible biomaterials that provide necessary support for these cardiovascular progenitors. Furthermore, we have already shown in several previous works, the clear therapeutic benefit of this approach. 

Since 2011, to achieve these objectives, we have built a multidisciplinary consortium which involves three laboratories (team Prof. Philippe Menasche, Inserm U970; team Prof. Jérôme Larghero, Cell Therapy Unit of St. Louis Hospital and team Dr. Yong Chen, ENS, Paris) and a company (Biom’up, Lyon) which have an expertise in a complementary fields. 

In conclusion, the aim of the "Stem Cells and Biotherapies" team, using multidisciplinary approaches, is to raise technical obstacles limiting the success of cardiac engineering in order to use this approach as well as in fundamental research and for biomedical applications.

Collaborations
  • Dr. Gillian Butler-Browne (Laboratoire Thérapies des maladies des muscles striés, UMR_S 974 Inserm/UPMC, Paris)
  • Pr. Louis Casteilla et Dr. Valérie Planat (UMR 5273 UPS, CNRS, EFS, Inserm U1031, STROMALab, Toulouse)
  • Dr. Yong Chen (ENS Paris, CNRS UMR 8640, Paris)
  • Dr. Yong Chen (Institute for Integrated Cell-Material Sciences, Kyoto University, Japan)
  • Dr. Catherine Coirault (Laboratoire Thérapies des maladies des muscles striés, UMR_S 974 Inserm/UPMC, Paris)
  • Pr. Thierry Delair (Laboratoire Ingénierie des Matériaux Polymères, CNRS UMR 5223, Lyon)
  • Dr. Julie Dumonceaux (Laboratoire Thérapies des maladies des muscles striés, UMR_S 974 Inserm/UPMC, Paris)
  • Pr. Arnaud Ferry (Laboratoire Thérapies des maladies des muscles striés, UMR_S 974 Inserm/UPMC, Paris)
  • Dr. Patricia Forest (Société pharmaceutique Biom’Up, Lyon)
  • Dr. Christophe Hourdé (Université Savoie, Chambery)
  • Pr. Jérôme Larghéro (Unité de Thérapie Cellulaire de l’Hôpital Saint Louis, Paris)
  • Dr. Zhenlin Li (Laboratoire Adaptation Biologique et Vieillissement, CNRS UMR 8256, Paris)
  • Pr. Christophe Magnan (Laboratoire Biologie Fonctionnelle et Adaptative, CNRS UMR 8251, Paris)
  • Pr. Philippe Menasché (Paris Centre de Recherche Cardiovasculaire, INSERM U970, Paris)
  • Pr. Fernando Rodrigues-Lima (Laboratoire Biologie Fonctionnelle et Adaptative, CNRS UMR 8251, Paris)
  • Pr. Guy Schlatter (Institut de Chimie et Procédés pour l’Energie, l’Environement et la Santé, CNRS UMR 7515, Strasbourg)
  • Pr. Patrick Vicart (Laboratoire Biologie Fonctionnelle et Adaptative, CNRS UMR 8251, Paris)
  • Dr. Claire Wilhelm (Laboratoire Matière et Systèmes Complexes, CNRS UMR 7057, Paris)