Device encapsulated MSCs for adaptive secretome therapy to effectively target ischaemic heart injury

• Encapsulated iPSC-derived MSCs in an immunoisolation device provide sustained secretome delivery, significantly improving cardiac function and reducing adverse remodelling over 12 weeks in rat models of chronic ischaemia-reperfusion injury. • The device maintains MSC viability and therapeutic secretome release for at least 12 weeks post-implantation, demonstrating a clinically translatable approach for long-term cardioprotection. • MSC secretome protects human engineered cardiac microtissues from simulated ischaemia-reperfusion injury by restoring contractile function, enhancing cell viability, and reducing oxidative stress. • Proteomic analysis reveals adaptive changes in encapsulated MSCs, with increased secretion of proteins involved in tissue repair and immune regulation, highlighting a dynamic response to ischaemic conditions.