STEM CELLS DISEASE MODELING

Patient heart on the dish – modeling inherited cardiomyopathy using stem cells

Mgr. Vladimír Rotrekl, Ph.D.

  • We discovered novel mechanism of heart failure in inherited cardiomyopathy
  • We model cardiomyopathy using patient specific stem cells.
  • We discovered novel DNA repair pathway in stem cells.

Research focus
The Stem Cell and Disease Modeling research team (SCDM) builds on long term experience with human pluripotent stem cells, their cultivation and their differentiation. The current focus of the team aims at the use of human pluripotent stem cells to model human diseases, which lead to cardiomyopathy and heart failure. A special focus is put upon progressive cardiomyopathies caused by cardiac progenitor depleti­on and heart remodeling due to cardiac progenitor genome instability. The SCDM uses reprogrammed human patient cells, as well as human embryonic stem cells with edited genome, to create models of monogenic diseases involving cardiomyopathy. The team also complements stem cell based modeling with the analysis of both animal models and human samples. The SCDM team has also developed novel technology to analyze mechanoelectrical coupling in stem cell derived patients, specifically cardiac syn­cytium based on atomic force microscope.

Research objectives

• To determine the extent and mechanisms of heart progenitor depletion in human DMD patients using patient specific hiPSCs.

• To characterize novel DNA repair pathways in human pluripotent stem cells and determine the effect of its failure on the depletion of stem cells in human progressive heart failure with delayed onset (using DMD model).

• To determine the mechanism of autocrine and paracrine signaling of basic fibroblast growth factor in pluripotent stem cells.

Main partners

• University of Montpellier, Montpellier, France

• University of Texas, San Antonio, TX, USA

• University Medical Center Göttingen, Göttingen, Germany