Considerations in designing systems for large scale production of human cardiomyocytes from pluripotent stem cells

Chen, Allen; Ting, Sherwin; Seow, Jasmin; Reuveny, Shaul; Oh, Steve

doi:10.1186/scrt401

Stem Cell Research & Therapy

Table 1 Methods for cardiomyocyte differentiation from human pluripotent stem cells, ranked by purity of yields

From: Considerations in designing systems for large scale production of human cardiomyocytes from pluripotent stem cells

hPSC expansion platform	Cardiomyocyte differentiation platform	Biomolecules	Purity	Scalability	Comments	Reference
Monolayer on feeders or Matrigel	Monolayer	Activin A, BMP4, VEGF, SCF, WNT3a	24% (Nkx 2.5)	+		[25]
		BMP2, 5% FBS	41.6% (cTnT)	+		[30]
		Activin A, BMP4	51% (MHC)	+		[10]
		Activin A, BMP4, DKK1	54.2% (cTnT)	+		[31]
		Activin A, BMP4, FGF2 , VEGF, DKK1	57.2% (cTnT)	+		[32]
		Activin A, BMP4	60% (α-actinin)	+		[33]
		Activin A, BMP4, IWP-4 or IWR-1	60.6% (MHC)	+		[34]
		Activin A, BMP4, FGF2, Noggin, BMS-189453, DKK1	73.0% (cTnT)	+		[35]
		BMP4, ascorbic acid, CHIR99021, IWR-1	80% (cTnT)	+		[36]
		Activin A, BMP4, FGF2	80% (cTnT)	+		[27]
		Activin A, BMP4, VEGF	85.4% (cTnT)	+		[37]
		CHIR99021, IWP-2/IWP-4	88.3% (cTnT)	+		[38]
		FBS	90% (cTnT)	+		[39]
		CHIR99021, BIO, KY02111, XAV939	97.7% (cTnT)	+		[40]
	Embyoid bodies	Activin A, FGF2	23.6% (beating EBs)	++	Forced aggregation	[41]
		Normoxic	48.3% (beating EBs)	++	Micropatterned; controlled bioreactor	[42]
		BMP4	95.8% (beating EBs)	+	Replated after 4 days	[43]
		Ascorbic acid	6.94% (cTnT)	+	Replated after 5 days	[44]
		BMP4, IWP-1	15.6% (cTnT)	+	Replated after 4 days	[45]
		SB203580	16% (MHC)	++		[28]
		SB203580	22.0% (MHC)	++		[46]
		BMP2, 5-azacytidine	23.7% (cTnT)	+	Replated after 6 days	[47]
		SB203580	26% (MHC)	++		[48]
		Activin A, BMP4, FGF2, VEGF, SCF	26.8% (Nkx 2.5)	++	Forced aggregation	[24]
		Activin A, BMP4, FGF2, VEGF	27.1% (MHC)	+	Replated after 4 days	[49]
		Activin A, BMP4, FGF2, VEGF, DKK1	37.2% (cTnT)	++		[50]
		WNT3a	50% (α-actinin)	+	Replated after 6 days	[51]
		BMP2	53.3% (cTnT)	++		[52]
		CHIR99021, IWP-2	60% (cTnT)	++		Unpublished data
		Activin A, BMP4, FGF2, VEGF, DKK1	60.2% (cTnI)	++		[53]
		Activin A, BMP4, FGF2 , VEGF, DKK1	82% (cTnT)	++		[23]
		BMP4,FGF2	82.3% (cTnI)	++	Forced aggregation	[54]
		Activin A, BMP4, FGF2, VEGF,DKK1	91.6% (cTnT)	++	Dissociated EBs	[55]
	Microcarriers	SB203580	20% (MHC)	+++		[28]
Cell aggregate	Monolayer	Activin A, BMP4, FGF2	80% (cTnT)	+		[27]
	Embryoid bodies	Activin A, BMP4, FGF2, VEGF, DKK1	27% (cTnT)	+++		[56]
		BMP4	36.9% (Nkx 2.5)	+	hESC encapsulation	[57]
		Activin A, BMP4, FGF2, VEGF, IWR-1	80% (cTnT)	+++	Controlled bioreactor	[27]
	Microcarriers	No data
Microcarriers	Microcarriers	CHIR99021, IWP-2	67% (cTnT)	+++		Unpublished data

BMP, bone morphogenetic protein; cTnI, cardiac troponin I; cTnT, cardiac troponin T; EB, embryoid body; FBS, fetal bovine serum; FGF, fibroblast growth factor; hESC, human embryonic stem cell; hPSC, human pluripotent stem cell; MHC, myosin heavy chain; SCF, stem cell factor; VEGF, vascular endothelial growth factor.

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ISSN: 1757-6512

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