UNS: Development of a Micropost Approach for the Contractile Maturation of iPS-Derived Cardiomyocytes

University Of Washington, Seattle WA

Investigators

Abstract

PI: Sniadecki, Nathan J. Proposal Number: 1509106 The goal of this project is to develop a novel strategy that improves the functionality of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) in culture. Human induced pluripotent stem cells are not harvested from embryos, which means they can serve as a noncontroversial and plentiful source of cardiomyocytes. These cells have the potential to be used to reverse the damage to cardiac tissue caused by heart attacks, assess new pharmacological treatments for heart disease, and serve as a model system for studying heart development. To unlock the potential of hiPSC-CMs, this project will evaluate the effects of mechanical cues like substrate stiffness, cell shape, cyclic strain, and cell-cell contact in combination with biochemical treatments that promote cardiac maturation. The expected outcome of this project is an effective approach for in vitro culture of hiPSC-CMs that can be widely adopted. The lack the contractile power and maturation markers for hiPSC-CMs is a major challenge to overcome in order for these cells to be used effectively as a source of new cardiomyocytes. To address this challenge, the efforts in this project are centered on using arrays of flexible microposts for evaluating the contractile forces of hiPSC-CMs and quantitative fluorescence microscopy techniques to assess their myofibril structure, hypertrophy, isoform expression, and calcium handling. Tasks 1 and 2 of this project focus on studying the mechanical cues that improve the contractility and maturation of hiPSC-CMs, including cell alignment, cell-cell contact, extracellular stiffness, and applied strain. Task 3 examines the effectiveness of these mechanical cues alongside biochemical treatments that are related to cardiac development. The broader impacts of this work lie in the potential advancement of new cardiac therapies, drug screening, and developmental studies. In addition, the project has educational and outreach components that will impact the training and career development of future engineers who will work at the interface between engineering, cardiology, and developmental biology.