TABLE 1.
Preclinical studies using hPSC‐derived neuronal cells
| Cell product | Disease | Registration no./program name | Reference | In vitro study | Animal | In vivo study |
|---|---|---|---|---|---|---|
| hiPSC‐derived dopaminergic progenitors | PD | R000038278 | Kikuchi et al 73 and Doi et al 34 | Marker expression; differentiation ability; electrophysiological analysis; dopamine release; genome analysis; single‐cell analysis; residual plasmids; residual pluripotent cells; mycoplasma; endotoxin; sterility | NOG mice; 6‐OHDA‐lesioned nude rat; MPTP‐lesioned monkey | Marker expression; toxicity; tumorigenicity; biodistribution; graft size; imaging (MRI, PET‐CT); efficacy |
| hiPSC‐derived neural stem/progenitor cells | SCI | jRCTa031190228 | Nakamura et al 74 and Nori et al 75 | Marker expression; differentiation ability; electrophysiological analysis | SCI in NOD/SCID mice | Marker expression; cell tracing; tumorigenicity; synapse connection; cell counting; efficacy |
| Human parthenogenetic ESC‐derived dopaminergic neurons | PD | NCT03119636 | Wang et al 37 | Marker expression; electrophysiological analysis; differentiation ability; residual pluripotent cells; mycoplasma; endotoxin; bacteria and fungi | SCID mice; MPTP‐lesioned monkey | Marker expression; cell counting; tumorigenicity; blood biochemistry; cell tracing; graft size; dopamine release; imaging (MRI); efficacy |
| Human parthenogenetic ESC‐derived neural stem cells | PD | NCT02452723 | Gonzalez et al 76 and Garitaonandia et al 38 | Marker expression; differentiation ability; bacteria and fungi; mycoplasma; karyotype; residual pluripotent cells; RNA‐seq | Nude rat; MPTP‐lesioned monkey | Marker expression; cell counting; tumorigenicity; biodistribution; efficacy |
| hESC‐derived astrocytes | ALS | NCT03482050 | Izrael et al 24 | Marker expression; differentiation ability; karyotype; pluripotent cells residuals; biological functionality | SOD1G93A transgenic mice and rats; immunodeficient NSG mice | Marker expression; cell counting; tumorigenicity; biodistribution; efficacy |
| hESC‐derived oligodendrocyte progenitors | SCI | NCT02302157 | Priest et al 41 | Marker expression; differentiation ability; sterility; mycoplasma; biological functionality | Thoracic SCI athymic nude rats; Shiverer/Rag2 mice; SCID/Bg mice | Marker expression; tumorigenicity; biodistribution; efficacy |
| Human autologous iPSC‐derived dopaminergic progenitors | PD | — | Song et al 44 | Marker expression; differentiation ability; karyotype; electrophysiological analysis; residual pluripotent cells; residual plasmids; dopamine release; genome analysis; mycoplasma | NOD/SCID mice; Athymic rats; 6‐OHDA‐lesioned athymic rats | Marker expression; cell counting; tumorigenicity; biodistribution; efficacy |
| hESC‐derived dopaminergic progenitors | PD | STEM‐PD trial | Kirkeby et al, 54 Nolbrant al, 45 Tiklova et al, 67 and Grealish et al 20 | Marker expression; differentiation ability; electrophysiological analysis; residual pluripotent cells; mycoplasma; endotoxin; sterility; single‐cell analysis | 6‐OHDA‐lesioned rats; athymic “nude” rats | Marker expression; cell counting; graft size; tumorigenicity; biodistribution; predictive biomarkers; imaging (MRI, PET‐CT); efficacy |
| hESC‐derived dopaminergic progenitors | PD | NCT04802733 | Kikuchi et al, 73 Nakamura et al, 74 Kriks et al, 77 and Ganat et al 29 | Marker expression; differentiation ability; residual pluripotent cells; mycoplasma; endotoxin; electrophysiological analysis; dopamine release; RNA‐seq; sterility | 6‐OHDA‐lesioned mice/rat; SCID mice; MPTP‐lesioned monkey | Marker expression; cell counting; graft size; biodistribution; toxicology; tumorigenicity; efficacy |
Abbreviations: ALS, amyotrophic lateral sclerosis; ESC, embryonic stem cells; hESC, human embryonic stem cells; hiPSC, human induced pluripotent stem cells; hPSC, human pluripotent stem cells; MRI, magnetic resonance imaging; MPTP, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine; NOD, non‐obese diabetes; NSG, NOD‐SCID IL2rg‐/‐; PD, Parkinson's disease; PET‐CT, Positron Emission Tomography‐Computed Tomography; SCI, spinal cord injury; 6‐OHDA, 6‐hydroxydopamine.