Engineering epicardium-integrated human iPSC-derived heart tissue for modelling Hutchinson-Gilford Progeria Syndrome [Infinium Methylation EPIC]

Engineered heart tissues (EHT) have been utilized in research for almost three decades and have become an important tool in cardiovascular research to address the shortcomings of the interspecies issues of animal models and oversimplicity of single cell type two-dimensional cell models to recapitulate cardiac (patho)physiology. Recently, epicardium-integrated EHT models have emerged in research as therapeutic applications for remuscularizing the failing heart.

Epicardium is the outermost mesothelial layer of the heart and plays a central role in heart development and pathophysiology. It acts as a source of progenitor cells, thus contributing to cardiac fibroblast (CF), vascular smooth muscle cell (VSMC) and pericyte populations in heart, and participates in essential signaling by secreting factors guiding cardiomyocyte growth and maturation. In this study, we developed an epicardium-integrated EHT to allow more physiologically relevant modelling of Hutchinson-Gilford Progeria Syndrome (HGPS), a laminopathy caused by a single point mutation in LMNA gene leading to expression of truncated Lamin A protein called progerin.