Title:

An Engineered Culture System for Human Cardiac Syncytium: Structural, Mechanical, and Electrical Readouts of Heart Cells in a Dish

Speaker:

Dr. Wendy Crone

Affiliation:

University of Wisconsin-Madison

When:

Thursday, September 22, 2022 at 2:00:00 PM   Add to Calendar

Where:

MRDC Building, Room 4211

Host:

Min Zhou and Shuman Xia
min.zhou@gatech.edu and shuman.xia@me.gatech.edu

Abstract

Human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) have emerged as an exciting new tool for cardiac research and can serve as a pre-clinical platform for drug development and disease modeling studies. However, these aspirations are limited by current culture methods in which hPSC-CMs resemble fetal human cardiomyocytes in terms of structure and function. The Crone Lab has produced a novel platform for use with hPSC-CMs and human pluripotent stem cell-derived cardiac fibroblasts (hPSC-CFs), that includes patterned extracellular matrix (ECM) with physiological substrate stiffness to enhance these cells for in vitro studies. The platform is amenable to structural, mechanical, and electrical characterization. Interrogation of the mechanical function of the pattern constructs using digital image correlation (DIC) demonstrates the utility of this platform for mechanical characterization of coordinated contractions. Micropatterned lanes promote the cellular and myofibril alignment of hPSC-CMs while the addition of micropatterned bridges enable formation of a functional cardiac syncytium that beats synchronously over a large 2D area within the platform. Investigation of electrophysiological properties of the patterned cardiac constructs with optical mapping shows that they have anisotropic electrical impulse propagation, as occurs in the native myocardium. Additionally, when iPSC-CFs are confined to the micropatterned features of the platform they remodel the ECM into anisotropic fibers. Our results also show that iPSC-CFs influence iPSC-CM function with accelerated Ca2+ transient rise-up time and greater contractile strains in the co-culture conditions compared to when iPSC-CMs are cultured alone. We also demonstrate the utility of this platform to investigate disease models.

Biography

Wendy C. Crone is the Karen Thompson Medhi Professor in the Department of Engineering Physics at the University of Wisconsin–Madison. She holds affiliate faculty appointments in the Departments of Biomedical Engineering and Materials Science and Engineering and the title of Discovery Fellow with the Wisconsin Institute for Discovery. Her research is in the area of solid mechanics, and many of the topics she has investigated are connected with biotechnology and nanotechnology. She has applied her technical expertise to improving fundamental understanding of mechanical response of materials, enhancing material behavior through surface modification and nanostructuring, exploring the interplay between cells and the mechanics of their surroundings, and developing new material applications and medical devices. Her research has been funded by the National Institutes of Health, National Science Foundation, Department of Energy, Air Force Office of Scientific Research, DARPA and the Whitaker Foundation. Prof. Crone has been recognized with numerous awards for research, teaching and mentoring, and is a Fellow of the Society for Experimental Mechanics. She has served in several leadership roles at UW-Madison, including prior appointments as Interim Dean and Associate Dean of the Graduate School, and Associate Chair in the Department of Engineering Physics. In addition to numerous publications and several patents, Prof. Crone is the author of two books, Survive and Thrive: A Guide for Untenured Faculty and Introduction to Engineering Research.

This seminar is co-sponsored by CoE Dean's Office and Woodruff School of ME.