Hydrogel‐Sheathed hiPSC‐Derived Heart Microtissue Enables Anchor‐Free Contractile Force Measurement

Abstract

In vitro reconstruction of highly mature engineered heart tissues (EHTs) is attempted for the selection of cardiotoxic drugs suitable for individual patients before administration. Mechanical contractile force generated in the EHTs is known to be a critical indicator for evaluating the EHT response. However, measuring contractile force requires anchoring the EHT in a tailored force‐sensing cell culture chamber, causing technical difficulties in the stable evaluation of contractile force in long‐term culture. This paper proposes a hydrogel‐sheathed human induced pluripotent stem cell (hiPSC)‐derived heart microtissue (H3M) that can provide an anchor‐free contractile force measurement platform in commonly used multi‐well plates. The contractile force associated with tissue formation and drug response is calculated by motion tracking and finite element analysis on the bending angle of the hydrogel sheath. From the experiment of the drug response, H3M is an excellent drug screening platform with high sensitivity and early testing capability compared to conventionally anchored EHT. This unique platform would be useful and versatile for regenerative therapy and drug discovery research in EHT.

Scalable production of homogeneous cardiac organoids derived from human pluripotent stem cells

“…In the field of cardiology, 3D tissue engineering techniques can induce the maturation of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs), overcoming one of the main challenges of hiPSC-CMs, which is their immaturity. 3 , 4 , 5 Notably, scaffold-free 3D models such as cardiac spheroids (CSs) and cardiac organoids (COs) self-assemble, are easy to fabricate, and do not require specific equipment. As an established disease model, COs with hypoxia and chronic adrenergic stimulation have been reported to recapitulate the structure and function of myocardial ischemia.…”