Specific Blood Cells Derived from Pluripotent Stem Cells: An Emerging Field with Great Potential in Clinical Cell Therapy

Table 1

Selected reports for the functional blood cells derived from PSCs.

Cell source	Methods	Factors	Generated cells	Specific markers	Production efficiency	Functional assessment	Reference
Mouse (MHC-I-restricted OVA TCR, OT1)-inducible Runx1-p2a-Hoxa9-induced pluripotent stem cells	EB formation and coculture with OP9-DL1 for OT1-iHPC generation and T lymphocyte reconstitution in vivo	BMP-4, VEGF, AFT024-mIL3, AFT024-mIL6, AFT024-mSCF, AFT024-mFlt-3L, iron-saturated transferrin, monothioglycerol, ascorbic acid	OT1-iT cells	CD8	~9.1% in PB	Effectively eradicated E.G7-OVA tumor cells in vivo	52
Mouse pluripotent stem cells	EB formation and coculture with OP9-DL1 for iHPC generation and T lymphocyte reconstitution in vivo and then isolated and infected with the CD19-CAR	BMP-4, VEGF, AFT024-mIL3, AFT024-mIL6, AFT024-mSCF, AFT024-mFlt-3L, iron-saturated transferrin, monothioglycerol, ascorbic acid	CD19-CAR-iT cells	CD3, CD4, and CD8	CD3^+CD4^+63.2%; CD3^+CD8^+35.3% in spleens	Efficiently eliminated B lymphoma cells Ka539 in vivo and in vitro	53
Mouse inducible HoxB4 embryonic stem cells	EB formation and coculture with OP9 stromal cells	Recombinant KL, IL-6, IL-3, TPO, VEGF, Flt-3L, and M-CSF	MDSCs	CD115, Ly-6C	53.9%	Prevented GVHD following allogeneic bone marrow transplantation	61
Mouse-induced pluripotent stem cells	Coculture with OP9 stromal cells and hepatic stellate cells	GM-CSF	MDSCs	CD11b, CD80, CD86 and B7-H1	Upto 80% CD11b^+CD11c^low/−and 20% CD11b^+CD11c^high	Regulated T cell responses in vitro and in vivo and diminished CD8+ T cell infiltration and ALT leakage in an autoimmune hepatitis murine model	65
Human-induced pluripotent stem cells; Human embryonic stem cells	Coculture with OP9 stromal cells for hematopoietic differentiation and isolated CD235a/CD41a^–CD45^+ for myeloid progenitors generation	M-CSF, IL-1β	Macrophages	CD115, CD163, CD14, and CD68	35%~44%	The ability of a self-quenched conjugate of ovalbumin (DQ-OVA) uptake, processing, and allogeneic stimulation	69
Human-induced pluripotent stem cells	In earlier stage: coculture with OP9 stromal cells; in later stage: cultured in the presence of GM-CSF and M-CSF without OP9 cells	GM-CSF, M-CSF	Macrophages	CD11b, CD14 and CD68	Unmentioned	Ingested both immunoglobulin G-opsonized and unopsonized zymosan particles and showed chemotactic response to C5a. Inhibited the growth of BALL-1 cells in vivo and in vitro	70
CAR-expressing human-induced pluripotent stem cells	EB formation	BMP-4, bFGF, VEGF, SCF, IGF-1, IL-3, M-CSF, and GM-CSF	CAR-macrophages	CD11b, CD14, and CD163	~100% of CD11b and CD14 expression	Inhibited CD19-expressingK562 or leukemia cells mesothelin-expressing OVCAR3/ASPC1 ovarian/pancreatic cancer cells in vitro and ovarian cancer cells HO8910 in vivo	74
Human embryonic stem cells	Coculture with mouse bone marrow stromal cell line S17 and cocultured with AFT024 stromal cells	Ascorbic acid, 2-ME, IL-15, IL-3, IL-7, Flt-3L, and SCF	NK cells	CD56	About 30%~40% on day 28	Showed significant cytolytic activity to K562 cells in vitro and upregulate IFN-γ production in response to IL-12/IL-18 stimulation	86
Human embryonic stem cells and induced pluripotent stem cells	Spin EB formation	BMP-4, bFGF, VEGF, IL-15, IL-3, IL-7, Flt-3L, and SCF	NK cells	CD45, CD56	>90%	Killed against K562 cells and MOLM13 cells in vitro	87
Human embryonic stem cells and induced pluripotent stem cells	Completely chemically defined condition in two-dimensional culture	BMP-4, VEGF, IL-15, IL-7, Flt-3L, and SCF	NK cells	CD56		Killed K562 cells in vivo and in vitro	88
Human embryonic stem cells	Cocultured with C3H10T1/2 or OP-9 cells	IL-6, IL-11, SCF, TPO, and heparin	Platelets	CD41a, CD42b	Most small particles positive for CD41a and CD42b	Displayed integrin αIIbβ3 activation and spreading in response to ADP or thrombin	100
Human embryonic stem cells and induced pluripotent stem cells	Serum/feeder-free conditions	BMP-4, bFGF, VEGF, TPO, SCF, Flt-3L, IL-3, IL-6, IL-9, and heparin	Platelets	CD41a, CD42b	>80%	Formed aggregates, lamellipodia, and filopodia after activation in vitro and thrombus in vivo	101
Human embryonic stem cells	EB formation in a 3D CellSTACK culture chamber	AA2P, BMP-4, bFGF, CHIR99021, VEGF, SB431542, SCF, TPO, IL-3, Flt-3L, IGF1, GM6001, and IL-11	Platelets	CD41a, CD42b, and CD61	>80% coexpressed with CD41a and CD61 and >50% coexpressed with CD41a and CD42b	Showed increased CD62P expression and clot aggregation after thrombin activation	102
Human-induced pluripotent stem cells	EB formation	SCF, TPO, FLT-3L, BMP4, VEGF, IL-3, IL-6, and EPO	RBCs	CD235a and CD71	hiPSCs gave rise to up to mature erythroid cells	CO flash photolysis experiments confirmed that the hemoglobin F in cultured RBC is functional	104
Human-induced pluripotent stem cells	EB formation	Holotransferrin, plasma, SCF, IL-3, EPO, and insulin	RBCs	CD36 and GPA	CD36 (>90%) and GPA ()	HPLC revealed the presence of predominantly fetal hemoglobin in hiPSC-derived RBCs	105