Abstract
Characterization of cardiomyocyte beat patterns is needed for quality control of cells intended for surgical injection as well as to establish phenotypes in disease modeling or toxicity studies. Optical-flow based analysis of videomicroscopic recordings offer a manipulation-free and efficient characterization of contractile cycles, an important characteristics of cardiomyocyte phenotype. We demonstrate that by appropriate computational analysis of optical flow data one can identify distinct contractile centers and distinguish active cell contractility from passive elastic tissue deformations. Our proposed convergence measure correlates with myosin IIa immuno-localization and is capable to resolve contractile waves and their synchronization within maturing, unlabeled induced pluripotent stem cell-derived cardiomyocyte cultures.
Highlights
Heart diseases are the leading cause of death in the United States and around the world1
We have formulated a combinatorial, safe, animal-free and viral-free approach using DNA and RNA pluripotent factors that can reprogram a wide range of adult human cells into induced pluripotent stem cells (iPSCs)–with subsequent differentiation into functional cardiomyocytes6
Recent studies have shown that iPSC-derived cardiomyocytes yield an adult phenotype through a maturation process7, 8
Summary
Heart diseases are the leading cause of death in the United States and around the world. Medical-grade, induced pluripotent stem cell (iPSC)-derived cardiomyocytes are promising both as implants to improve cardiac function and as tools to model cardiac diseases. Myocardial tissue repair using iPSC-derived cardiomyocytes, reprogrammed from a patient’s somatic cells by mechanisms analogous to those taking place during embryonic development, is a promising avenue for future treatment of cardiac diseases. Recent studies have shown that iPSC-derived cardiomyocytes yield an adult phenotype through a maturation process7, 8 While these studies were primarily focused on electrophysiological end-points, the most important characteristic of a cardiomyocyte, is its ability to contract. By considering the mechanics of an elastic plate with an embedded contractile center, we propose novel image-processing tools to monitor and evaluate the contractility of reprogrammed, iPSC-derived cardiomyocytes in high cell density culture conditions. We demonstrate that our contractility measure identifies cardiomyocyte clusters with high myosin expression, and it can track culture maturation by determining the extent of spatial synchronization
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