Table 5.

Key advances in hPSC-epicardial differentiation.

Initial cell type	Bioactive factors	Culture	Key advances	Refs
hESC, iPSC	rhBMP4, rhActivin A, rhbFGF, rhDKK1, SB431542, rhVEGF, CHIR99021, XAV-939, PD-173074	EB, monolayer	Identified BMP and WNT as key regulators of the epicardial lineage in vitro.	2014, Witty et al. [98]
hESC, iPSC	FGF2, LY294002, BMP4, WNT3A. RA, IWP2	monolayer	Described a chemically defined method for generating epicardium and epicardium-derived smooth muscle cells and cardiac fibroblasts from hPSCs through an intermediate lateral plate mesoderm (LM) stage.	2015, Iyer et al. [97]
hESC, iPSC	CHIR99021, IWP2, A83-01 or SB431542	monolayer	Chemically-defined, xeno-free method of generating epicardial cells from hPSCs by modulating Wnt signaling. And TGF-β inhibition allows long-term expansion of hPSC-derived epicardial cells.	2016, Bao et al. 2017, Bao et al. [99,101]
hESC, iPSC	CHIR99021, IWR1, RA	monolayer	A chemically defined, immunogen-free, small molecule-based method for generating TBX18+/WT1+ epicardial-like cell populations with 80% homogeneity from hPSCs by modulation of the Wnt and retinoic acid signaling pathways.	2017, Zhao et al. [100]