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
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
- 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
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.
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.