Development of porous cellular scaffolds for cardiac stem cell therapy

Small equipment, AAP 2017-1

Team: Institut de Biologie Paris Seine, Team « Stem Cells and Biotherapies »

Project leader : Onnik Agbulut

Abstract:

Cardiovascular diseases are the leading cause of disability, limiting the activity and eroding the quality of life of millions of both middle-aged adults and elderly each year. It represents a growing global health problem that will reach epidemic proportions in an ageing and rapidly expanding global population. These observations have provided a rationale for exploring new therapeutic options, among which “regeneration” of the chronically failing heart by stem cells supported on biomaterials has raised a tremendous interest. 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 propose that 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 this issue, we propose to switch from mere cell therapy to a more composite tissue engineering construct entailing the use of human cardiac cells seeded into a biocompatible porous biomaterial. In this approach, cardiac cells will contribute to heart tissue regeneration while porous biomaterial will serve as structural and trophic support. The main objective of this project is therefore to take into account the current limitations of cell therapy and to design a new cell therapy product consisting of a porous biomaterial cellularized by cardiac cells allowing the formation of a micro-tissue. The graft will be done by depositing this product on the surface of the heart. In summary, at the interface of cell biology and biomaterials physics, this project will allow us to generate new data which will help overcoming current obstacles to success of cardiac cell therapy for which heart transplantation remains the only radical treatment.

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