Table 1.
Summary of generation and characterization of erythroid cells from human embryonic stem cells and induced pluripotent stem cells.
Authora | Stem cell lines | Method | Stromal cellsb | Major globin chains | Hb | Enu (%) | Yieldc | 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/Me | 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, γf | 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, OP9g | ζ, α, ε, γ | N/M | 10–30; 30–65h | 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,γf | 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.