Generation of human chambered cardiac organoids from pluripotent stem cells for improved modelling of cardiovascular diseases

Abstract

Recent progress on murine and human cardiac organoids have provided understanding to the developmental processes of the heart. However, there is still an unfulfilled need for improved modelling of cardiovascular diseases using human cardiac organoids. Herein, we report successful generation of intrinsically formed human chambered cardiac organoids (CCO) and highlight its utility in modelling disease. Single cell transcriptomic profiling of CCOs showed appropriate cardiovascular cell type composition exhibiting improved maturation. Functionally, CCOs recapitulated clinical cardiac hypertrophy by exhibiting thickened chamber walls, reduced ejection fractions, increased myofibrillar disarray and tachycardia. Therefore, CCOs improve current capabilities of disease modelling as an in vitro model bridging the gap to in vivo models, with the ability to assess functional parameters that previously can only be achieved in animal systems. One sentence summaryModelling cardiac hypertrophy using chambered cardiac organoids derived from human pluripotent stem cells.