Generation and Characterization of Erythroid Cells from Human Embryonic Stem Cells and Induced Pluripotent Stem Cells: An Overview

Table 1

Summary of generation and characterization of erythroid cells from human embryonic stem cells and induced pluripotent stem cells.

Author^a	Stem cell lines	Method	Stromal cells^b	Major globin chains	Hb	Enu (%)	Yield^c	Culture length (days)^d	Note	Ref.
Dias J.	H1, hiPSCs	coculture	OP9 → MS5	ε, γ	N/M	2–10	200,000	75		[8]
Kaufman DS.	H1	coculture	S17, C166, MEF	α, β, δ	N/M	N/M	N/M	42		[9]
Klimchenko O.	H1, H9	coculture	OP9 → MS5	ζ, ε	N/M	no	N/M	38		[10]
Lee KY.	H1, H9, H14	coculture	AGM, FL, FBM	α, γ, δ	N/M	no	N/M	32		[11]
Ledran MH.	H1, H9, hES-NCL1	coculture	AGM, FL	α, ε, γ	N/M	N/M	N/M	39		[12]
Ma F.	H1	Coculture	mFLSC	ε, γ, β	N/M	6.2	1,200	34	Time-dependent β globin increase at clonal level. Oxygen dissociation curve and G6PD activities are more similar to CB than to adult PB	[13]
Qiu C., Olivier EN.	H1	Coculture	FH-B-hTERT, S17	ζ, α, ε, γ	N/M^e	1.5-16	80	59	Maturation switch and lineage switch noted. Minor increase in β globin expression	[1, 14, 15]
Cerdan C.	H1, H9	EB	N/A	ε, β	HbA > HbF	N/M	N/M	29		[16]
Chang KH.	H1, BG02, hiPSCs	EB	N/A	α, ε, γ	N/M	N/M	N/M	21		[17–19]
Lapillonne H.	H1, hiPSCs	EB	N/A	α, γ	HbF	4–66	200–3,500	46	CO rebinding kinetics similar to CB	[20]
Zambidis ET.	H1	EB	N/A	ζ, α, ε, γ ^f	HbF > HbA	N/M	N/M	36	Time-dependent increase in β globin expression observed. Primitive to definitive switch noted	[21]
Lu SJ.	H1, MA01, MA99, HuES-3	EB → BL	MSC, OP9^g	ζ, α, ε, γ	N/M	10–30; 30–65^h	800–8,000	25	Oxygen dissociation curve slightly displaced to left of normal RBCs. Decreased response to 2,3-DPG depletion as compared to adult RBCs. Comparable Bohr effect at physiologic pH	[22]
Honig GR.	H1, H7, MA01	EB → BL	N/A		Hb Gower I > Hb Barts	N/M	N/M	25	Low (α + ζ)/(γ + ε) synthesis ratio	[23]
Liu YX.	H1	EB → coculture	hFLSC	ζ, α, ε,γ ^f	N/M	N/M	N/M	29	β globin expression increases with culture time. Oxygen dissociation curve slightly displaced to left of normal RBCs	[24]

^aPublications by the same laboratory are grouped together. ^bArrow indicates sequential exposure to different stromal cells. ^cNumber of erythroid cells generated per hESCs or hiPSCs. ^dCulture time is approximate as it is often variable even within one particular study. Culture length is for generating hemoglobinized erythroblasts and may not include time required for enucleation. ^eThe authors speculated the hemoglobin tetramer species based on globin chain results. ^fThe major globin chains expressed cannot be determined based on the method employed. ^gFor enucleation purpose only. ^hHigher enucleation efficiency is associated with stromal coculture. Hb: hemoglobin tetramer; N/M: not mentioned; Enu: enucleation; N/A: not applicable; CB: cord blood; PB: peripheral blood; BL: hemangioblasts; MSC: mesenchymal stem cells.