bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 15, 2024
Interactions between the developing heart and embryonic immune system are essential for proper cardiac development maintaining homeostasis, with disruptions linked to various diseases. While human pluripotent stem cell (hPSC)-derived organoids valuable models studying organ function, they often lack critical tissue-resident cells. Here, we introduce an advanced assembloid model, termed hHMA (human heart-macrophage assembloid), which fully integrates autologous tissue- resident macrophages (MPs) pre-existing (hHOs). Through multi-omic analyses, confirmed that these MPs phenotypically similar remain viable in assembloids over time. The inclusion of significantly impacts development, influencing cellular composition, boosting communication, remodeling extracellular matrix, promoting ventricular morphogenesis, enhancing sarcomeric maturation. Our findings indicate contribute homeostasis via efferocytosis, integrate into cardiomyocyte electrical system, support catabolic metabolism. To demonstrate versatility this developed a platform study arrhythmias by chronic exposure pro-inflammatory factors arrhythmogenesis clinical settings, successfully replicating key features inflammasome-mediated atrial fibrillation. Overall, work introduces robust examining role cells disease mechanisms, drug discovery, bridging gap
Language: Английский