Table 3 Summary of pre-clinical studies using clinical-grade cells for cell therapies against Parkinson’s disease.
Reference | Cellular product | Criteria | In vitro study | In vivo study | Number of animals | Cells/animal | Evaluation | Observation period |
|---|---|---|---|---|---|---|---|---|
Garitaonandia et al.10 | Human parthenogenetic stem cell-derived neural stem cells | NESTIN = 96.2% MSL1 = 93.5% SOX2 = 97.8% | Culture in ESC condition FCM QPCR | Nude rat | N = 15 N = 4 (control) | 2.5 × 106–7.7 × 106 | Acute toxicity | 7 days |
N = 80 N = 20 (control) | 2.5 × 105–7.7 × 106 | Tumorigenicity/ biodistribution | 9 months | |||||
Wang et al.11 | Human parthenogenetic ESC-derived DA neurons | TUJ1 = 99.8% TRA-1–60 = 0.1% SSEA-4 = 0.1% | Immunofluorescence FCM Electrophysiological analysis PCR | MPTP-treated monkey | N = 3 (FP), N = 4 (EB) N = 3 (control) | 2 × 106 | Tumorigenicity/efficacy | 9 months |
Nude mouse | Data not shown | Data not shown | Tumorigenicity | Data not shown | ||||
SCID mouse | Data not shown | Data not shown | Teratoma formation | 6 weeks | ||||
Present study | Human iPSC-derived dopaminergic progenitors | FOXA2/TUJ1 = 92.3% OCT4/TRA-2–49 < 0.1% SOX1/PAX6 < 0.1% | FCM QPCR Culture in iPSC condition Immunofluorescence Electrophysiological analysis DA measurement Genome/epigenome analysis Single-cell analysis | NOG mouse (brain) | N = 80 N = 50 (control) | 2 × 105 | Toxicity/tumorigenicity/ biodistribution | 12 months |
NOG mouse (subcutaneous) | N = 20 N = 60 (iPSC-spiked) N = 10 (negative control) N = 20 (positive control) | 6 × 105 | Teratoma formation | 6 months | ||||
6-OHDA-lesioned nude rat | N = 8 N = 6 (control) | 4 × 105 | Efficacy | 5 months | ||||
MPTP-treated monkey | N = 3 | 1.5 × 106–2.0 × 106 | Efficacy/tumorigenicity | 2–6 months |
