LEFTY-PITX2 signaling pathway is critical for generation of mature and ventricular cardiac organoids in human pluripotent stem cell-derived cardiac mesoderm cells

Designed peptide-grafted hydrogels for human pluripotent stem cell culture and differentiation

“…Human pluripotent stem cells (hPSCs), including human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs), have potential to differentiate into cells originating from 3 germ layers, the endoderm, ectoderm and mesoderm, which are promising for use as cell sources in regenerative medicine and stem cell therapy. 1–11 It is necessary to produce and maintain large amounts of hPSCs and their differentiated cells under xeno-free cultivation conditions for their usage in clinical applications. 12 The pluripotency maintenance and adequate differentiation of hPSCs into specific lineages of cells are regulated by cell cultivation biomaterials, whereby hPSCs are regulated by the physical and biological cues of cell culture biomaterials.…”

Induced pluripotent stem cell-based models: Are we ready for that heart in a dish?

“…A recent study has compared the ability of cardiac mesoderm cells and cardiomyocytes, derived respectively from 4 to 11 day of differentiation of hiPSCs, to generate cardiac organoids. This study found that the former protocol resulted in the improvement of structure, metabolism, function and overall maturation ( Song et al, 2021 ). In both cases, it is important to note that cardiac organoids arise from a single cell population that self-organizes, unlike cardiac spheroids which are assembled mixing different cell populations (cardiomyocytes, endothelial cells and fibroblasts) at defined ratios ( Polonchuk et al, 2017 ).…”

Proliferation and Maturation: Janus and the Art of Cardiac Tissue Engineering

“…Recent studies have shown that the LEFTY-PITX2 (left-right determination factor 1-paired-like homeodomain transcription factor 2) signaling pathway plays critical roles in the maturation process of cardiac organoids derived from hiPSC-cardiac progenitors. 158 Transcriptional profiling from these organoids revealed that ECM integrin, focal adhesion, and LEFTY-PITX2 signaling pathways are upregulated in these conditions. Further, they showed that LEFTY knockdown affected ECM-integrin-focal adhesion signaling pathways and demonstrated that LEFTY-PITX2 signaling plays key roles for cardiomyocyte maturation and specification into the ventricular-like cardiomyocyte subtype in cardiac organoids.…”

“…Further, they showed that LEFTY knockdown affected ECM-integrin-focal adhesion signaling pathways and demonstrated that LEFTY-PITX2 signaling plays key roles for cardiomyocyte maturation and specification into the ventricular-like cardiomyocyte subtype in cardiac organoids. 158 Maturation of cardiac organoids was also induced by a metabolic analog, 2-Cl-C.OXT-A in coculture of human dermal fibroblasts, hiPSCs, endothelial cells, and hiPSC-cardiomyocytes. 159 These studies support the importance of metabolites and paracrine factors in inducing cardiomyocyte maturation.…”