HUman STemcells for CArdiac REpair

Stem cell therapy for the heart is safe but has been most successful in improving cardiac function in clinical trials where preclinical research demonstrated activation of endogenous repair in the host heart tissue. Cardiac repair includes neovascularization and inflammation, endogenous cardiomyocyte and progenitor cell proliferation and differentiation. We hypothesize that deeper understanding of these mechanisms in animal models by directly comparing the effects of different stem cell types from different patients will lead to (i) identification of the best cell types and co-factors for therapy, and (ii) parameters that predict which patients are most likely to benefit from autologous versus heterologous cell transplantation. Candidate cells for comparison are mesenchymal stem cells (MSC) and cardiac stem cells (CSC). Candidate co-factors and mediators of paracrine mechanisms will include growth factors, delivered through slow release beads, and miRNAs that control differentiation. These factors have already been implicated as mediating endogenous cardiac repair; the goal here will be in examining their value in enhancing the effect of cell transplantation. We will not only use novel transgenic mouse models for these mechanistic and optimization studies but will also extend the investigation to pigs that have undergone myocardial infarction. Novel will be (i) investigation of the role of inflammation and the immune response on cardiac recovery following cell transplantation (ii) quantitative analysis of endogenous cardiac progenitor cell recruitment/cardiomyocyte proliferation (iii) determining the impact of CVD predisposition and gender in diagnostic bioassays to distinguish responding and non-responding patients retrospectively (iv) applying this information to ongoing and future trials.

Principal investigator(s): Pieter Doevendans en Hans Clevers

Started in: 2014

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