Mechanically induced pyroptosis enhances cardiosphere oxidative stress resistance and metabolism for myocardial infarction therapy

Abstract Current approaches in myocardial infarction treatment are limited by low cellular oxidative stress resistance, reducing the long-term survival of therapeutic cells. Here we develop a liquid-crystal substrate with unique surface properties and mechanical responsiveness to produce size-controllable cardiospheres that undergo pyroptosis to improve cellular bioactivities and resistance to oxidative stress. We perform RNA sequencing and study cell metabolism to reveal increased metabolic levels and improved mitochondrial function in the preconditioned cardiospheres. We test therapeutic outcomes in a rat model of myocardial infarction to show that cardiospheres improve long-term cardiac function, promote angiogenesis and reduce cardiac remodeling during the 3-month observation. Overall, this study presents a promising and effective system for preparing a large quantity of functional cardiospheres, showcasing potential for clinical application.