Table 1 Current strategies for the differentiation of functional hematopoietic cells from hPSCs.
Cell source | Methods | Main cytokines | Products | Functional Assessment | References | |
|---|---|---|---|---|---|---|
Human ESCs | EB formation | SCF, FLT-3L, IL-3, IL-6, G-CSF, BMP-4 | HSPCs | Self-renewal; multiple lineage progenitors in vitro | Chadwick et al. 2003 | |
Human ESCs | Co-culture with OP9, S17 or MS5 | SCF, FLT-3L, IL-7, IL-3 | HSPCs | Self-renewal; multiple lineages (including lymphoid lineage) in vitro | Vodyanik et al. 2005 | |
Human ESCs and iPSCs | Serum and feeder-free; 3D microcarrier and EB formation | VEGF, BMP-4, bFGF | HSPCs | Ten-times higher yields of hematopoietic cells than 2D culture; multiple lineage progenitors in vitro | Lu et al. 2013 | |
Human iPSCs | EB formation; 3D hemanoids | IL-3, M-CSF | HSPCs | Myeloid progenitors in vitro | Ackermann et al. 2021 | |
Human ESCs and iPSCs | Co-culture with OP9; HE formation | SCF, IL-3, IL-6, TPO | HSPCs | Hemogenic endothelial progenitor identification; multiple lineage progenitors in vitro | Choi et al. 2012 | |
Human ESCs and iPSCs | EB formation; HE formation | Seven TFs: ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1 | HSPCs | Multiple lineages (including lymphoid lineage) in vivo | Sugimura et al. 2017 | |
Human iPSCs | Co-injection with OP9; teratoma formation | In vivo | HSPCs | Reconstitute immune system (including lymphoid lineage) in primary and secondary recipients | Amabile et al. 2013 | |
Human iPSCs | HSPCs co-culture with OP9-DLL1 | FLT-3L, IL-7, IL-21 | T cells | Early memory phenotype and exert anti-viral/anti-tumor activity in vivo | Kawai et al. 2021 | |
Human iPSCs | HSPCs co-culture with ATOs and MS5 | SCF, FLT-3L, IL-7, TPO | T cells | Naïve phenotype and show anti-tumor in vitro and in vivo | ||
Human iPSCs | HSPCs co-culture with OP9-DLL1 | SCF, FLT-3L, IL-7, IL-15 | CAR-T cells | Innate γδ-T phenotype and exert anti-tumor activity in vivo | Themeli et al. 2013 | |
Human iPSCs | Serum and feeder-free | SCF, FLT-3L, IL-7, TPO, SDF-1α, SB203580 | CAR-T cells | TCR-dependent function and exert anti-tumor activity in vitro and in vivo | Iriguchi et al. 2021 | |
Human ESCs | HSPCs co-culture with AFT024 | SCF, FLT-3L, IL-7, IL-15, IL-3 | NK cells | Express inhibitory and activating receptors and lyse tumor cells in vitro and in vivo | ||
Human ESCs and iPSCs | HSPCs co-culture with EL08-1D2 or feeder-free; NK cells co-culture with aAPCs | SCF, FLT-3L, IL-7, IL-15, IL-3 | NK cells | Exert anti-tumor activity in vitro and in vivo | ||
Human iPSCs | NK cells co-culture with aAPCs | SCF, FLT-3L, IL-7, IL-15, IL-3 | CAR-NK cells | Mesothelin-specific CAR and anti-ovarian cancer with less toxicity in vivo | Li et al. 2018 | |
Human iPSCs | HSPCs co-culture with MS5 | SCF, FLT-3L, IL-7, IL-15, IL-3 | B cells | VDJ rearrangement in H chain and express surface IgM in vitro | ||
Human ESCs | Serum and feeder-free | SCF, IL-11, TPO | MKs and platelets | About 40% platelets in vitro and contribute to developing thrombi in vivo | Lu et al. 2011 | |
Human ESCs and iPSCs (GATA1, FLI1 and TAL1) | Serum and feeder-free | SCF, IL-1β, TPO | MKs and platelets | About 5 platelets per MK in vitro | Moreau et al. 2016 | |
Human ESCs and iPSCs (c-MYC, BMI1, BCL-XL) | Serum and feeder-free | SCF, TA-316, KP-457, SR1, GNF-351 | MKs and platelets | About 70–80 platelets per MK in vitro and show turbulence in thrombopoiesis in vivo | Ito et al. 2018 | |
Human ESCs and iPSCs | HSPCs co-culture with MS5 | SCF, IL-3, IL-6, TPO, EPO | Erythroblasts | Express α, ζ, ɛ, γ hemoglobin and enucleation | ||
Human ESCs and iPSCs | Serum and feeder-free | SCF, IL-3, EPO | Erythroblasts | Express α, β, ɛ, ζ, γ hemoglobin and enucleation | ||
Human ESCs and iPSCs | Serum and feeder-free | IL-3, M-CSF | Monocytes/Macrophages | Possess highly phagocytic function and release cytokines for stimulation in vitro; Polarize to M1 or M2 phenotype and improve liver fibrosis in vivo | ||
Human iPSCs | Feeder-free | SCF, IL-3, M-CSF, GM-CSF, IGF-1 | CAR-macrophages | Secrete cytokines, polarize to M1 phenotype, and anti-tumor in vivo | Zhang et al. 2020 | |
Human ESCs | HSPCs co-culture with OP9 | SCF, FLT-3L, IL-3, IL6, TPO, G-CSF | Neutrophils | Produce superoxide, phagocytose, engage in bactericidal activity, and chemotaxis in vitro; Recruit immune cells and against bacterial infection in vivo | ||
Human ESCs and iPSCs | Serum and feeder-free | SCF, IL-3, IL5 | Eosinophils | Express peroxidase and exert tumor killing capacity in vivo | Lai et al. 2021 | |
Human iPSCs | Serum and feeder-free | SCF, IL-3, IL-6, LDL | Mast cells | Express specific markers and degranulate in response to IgE/anti-IgE and substance P in vitro | Luo et al. 2022 | |