Table 1.
Generation and immunomodulatory properties of iPSC-derived APCs
| Cells to be generated | Cell source | Differentiation strategy |
In vitro functionality assays |
Ref. | ||||
|---|---|---|---|---|---|---|---|---|
| EBs | serum | basic stimuli | maturation/stimulation | proof of functionality | T-cell source | |||
| AP leukocytes | ESC | yes | FCS | SCF, Flt3-L, TPO, IL-3, GM-CSF and IL-4 | TNF-α, prostaglandin E2 | Elicit allogeneic T-cell responses in mixed lymphocyte reaction | Allogeneic | 24 |
| Dendritic cells | ESC | no | FCS | GM-CSF, M-CSF, IL-4 | IL-4, TNF-α, LPS, CD40L, OK-432 | T-cell stimulation, antigen presentation on HLA-II | Allogeneic | 26 |
| Dendritic cells | ESC | yes | human serum |
SCF, Flt3-L, GM-CSF, IL-3, TPO, IL-4, TNF-α | TNF-α, IL-1b, IL-6, prostaglandin E2, IFN-α2b, polyIC | Stimulating potent antigen-specific CD8+ T-cell responses | Semi-allogeneic | 28 |
| Dendritic cells | ESC | yes | no | BMP4, VEGF, SCF, GM-CSF, IL-4 | GM-CSF, TNF-α, IL-1β, IFN-γ and PGE2 | Activate both viral and tumor antigen-specific T-cell responses | Semi-allogeneic | 29 |
| Dendritic cells | ESC | no | FCS | SCF, FLT3-L, GM-CSF, TNF-α, IL-4, IFN-a | A23187 calcium ionophore | Induce allogeneic T-cell response | Allogeneic | 16 |
| Dendritic cells | iPSC | no | no | BMP4, VEGF, bFGF, SCF, FLt3-L, GM-CSF, IL-4 | Induce CEA-specific cytotoxic T cells and cytotoxicity | Autologous | 32 | |
| Dendritic cells/macrophages | iPSC | no | FCS | GM-CSF, M-CSF, IL-4 | IL-4, TNF-α, LPS, CD40L, OK-432 | Expand CMV-specific autologous CD8+ T cells | Autologous | 31 |
| Dendritic cells/macrophages | ESC & iPSC | no | FCS | GM-CSF, IL-4, TNF-α | TNF-α | Allo-stimulate T cells in mixed lymphocyte reaction | Allogeneic | 30 |
| Dendritic cells/macrophages | ESC & iPSC | no | no | BMP4, VEGF, SCF, bFGF, FLT3, TPO, IL-3, GM-CSF, IL-4 | TNF-α, LPS | Stimulate allogeneic T-cell proliferation | Allogeneic | 34 |
| cDC1 | iPSC | no | no | GM-CSF, SCF, VEGF, BMP4, IL-4 | TNF-α, PGE2, IFN-γ, IL-1b | Prime TAA-specific responses among naïve T cells | Allogeneic | 33 |
| cDC1, cDC2, pDC | ESC & iPSC | no | FCS | BMP4, bFGF, VEGF, SCF, IL-6, IGF, IL-3, TPO, Flt3, GM-CSF, IL-4 | LPS, CpG oligonucleotide, IL-3 | Mixed lymphocyte reaction | Allogeneic | 3 |
PSC, pluripotent stem cell; EB, embryoid body; ESC, embryonic stem cell; iPSC, induced pluripotent stem cell; FCS, fetal calf serum; AP, antigen presenting.