Heart-on-a-chip models of healthy and diseased myocardium

Description:
The new field of organ-on-a-chip engineering, relies on engineered, microfabricated, devices to drive establishment and measurement of critical physiological properties (e.g. contractility). My group has lead the way by a) defining an electrical stimulation protocol, in Nature Methods of ramping frequency increase (up to 6Hz) that enables iPSC-CM maturation; and as described in Cell by b) eliminating the use of drug absorbing PDMS; c) enabling non-invasive continuous measurement of contraction force by imaging; d) creating defined atrial, ventricular and atrioventricular tissues from human iPSC and e) modeling a polygenic cardiac disease, left ventricular hypertrophy, for the first time using cells from patients with high blood pressure who are enrolled in NIH HyperGen study. Critical for this success is the electrical field stimulation of iPSC-CM derived tissues using ramping frequency increase. In our initial experimental design, we ramped the frequency up to 3Hz expecting cell maturation, as heart rate peaks at 3Hz at 7 weeks gestation. Ramping the frequency to 6Hz was originally designed with the expectations that heart failure conditions will arise since pacing was too fast. Surprisingly, the data demonstrated superior cell maturation in the 6Hz vs 3Hz group. In a follow-up, we learned that we can achieve much needed atrial vs ventricular specification depending on how fast we ramp up the frequency to 6Hz (Fig. 3) and that we can build precious diseased heart muscles from patient iPSC if we stimulate long enough. In this presentation, I will present our most recent data on modelling covid19 induced myocarditis and testing of new molecules that prevent cytokine storm as well modelling cardiomyopathies resulting form ion channels and structural protein mutations. I will also show how to scale up the heart-on-a-chip device production by 3D printing and use PEDOT:PSS flexible conductive electrodes for recording of electrical impulses within the tissue.

Speaker: Milica Radisic - University of Toronto
Dr. Milica Radisic is a Professor at the University of Toronto, Tier 1 Canada Research Chair in Organ-on-a-Chip Engineering and a Senior Scientist at the Toronto General Research Institute. She is a Fellow of the Royal Society of Canada-Academy of Science, Canadian Academy of Engineering, the American Institute for Medical & Biological Engineering, Tissue Engineering & Regenerative Medicine Society as well as Biomedical Engineering Society. She received numerous awards and fellowships, including MIT Technology Review Top 35 Innovators under 35. She was a recipient of the Queen Elizabeth II Diamond Jubilee Medal in 2013, NSERC E.W.R Steacie Fellowship in 2014, YWCA Woman of Distinction Award in 2018, OPEA Research & Development Medal in 2019, Killam Fellowship in 2020 etc. Her research focuses on organ-on-a-chip engineering and development of new biomaterials. She developed new methods to mature iPSC derived cardiac tissues using electrical stimulation.