Table 2.
Peer-reviewed publications in NHP models of PD evaluating SCs as sources for dopaminergic cell replacement
| References | Host species | Cell species; graft type | Cell type | Cell labeling | Transplant location | Model | n | Immunosup. | l-DOPA | Behavioral test | PET imaging | Duration |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Takagi et al. (2005) | Cynomolgus (M. fascicularis) | Cynomolgus; allograft | ESC-derived DAergic progenitors | BrdU | Bilateral putamen; 3 tracts per side, each with 4 deposits | MPTP i.v. (0.4 mg/kg; twice weekly for 7 weeks) | 6 | CsA 10 mg/kg | None | Clinical rating | [18F]DOPA | 14 weeks |
| Cynomolgus (M. fascicularis) | N/A | Sham-operated | N/A | N/A | MPTP i.v. (0.4 mg/kg; twice weekly for 7 weeks) | 4 | CsA 10 mg/kg | None | Clinical rating | [18F]DOPA | 14 weeks | |
| Kikuchi et al. (2011) | Cynomolgus (M. fascicularis) | Human; xenograft | iPSC-derived DAergic progenitors | None | Bilateral putamen (d28 to right, d42 to left); 6 tracts per side, each with 4 deposits | MPTP i.v. (0.4 mg/kg; twice weekly until symptoms persisted) | 1 | FK506 0.05 mg/kg | None | Clinical rating, spontaneous movements, Gross Movements, Raisin pick-up test | [18F]DOPA, [11C]DTBZ, [11C]PE2I, [18F]FLT | 6 months |
| Daadi et al. (2012) | Green monkey (C. sabaeus) | Human; xenograft | ESC-derived DAergic progenitors | GFP | Caudate and SN | MPTP i.m. (2.25 mg/kg cumulative dose; administered over 5-day period) | 4 | CsA 5 mg/kg/day Prednisone 2 mg/kg tapering to 0.6 mg/kg/day Azathioprine 5 mg/kg/day reduced to 1 mg/kg/day | None | None | None | 2 months |
| Kriks et al. (2011) | Rhesus (M. mulatta) | Human; xenograft | ESC-derived DAergic progenitors | GFP | Bilateral posterior caudate, pre-commissural putamen and overlying white matter (GFP to one side, unmarked to other); 3 tracts per side | MPTP ICA (3 mg) followed by weekly i.v. administration (dose n.r.) | 2 | CsA 30 mg/kg tapered to 15 mg/kg | None | None | None | 1 month |
| Emborg et al. (2013b) | Rhesus (M. mulatta) | Human; xenograft | ESC-derived DAergic progenitors | GFP | Unilateral (ipsi-MPTP) rostral, medial and caudal caudate and putamen, and SN; 7 tracts total | MPTP ICA (3 mg) | 3 | CsA 40–50 mg/kg | None | None | None | 3 months |
| Emborg et al. (2013a) | Rhesus (M. mulatta) | Rhesus; autograft | iPSC-derived DAergic progenitors | GFP | Unilateral (ipsi-MPTP) precommisural and commissural caudate, pre-commisural, commissural and postcommisural putamen, and SN; 6 tracts total | MPTP ICA (3 mg) | 3 | None | None | None | None | 6 months |
| Wakeman et al. (2014b) | Green monkey (C. sabaeus) | Human; xenograft | ESC-derived DAergic progenitors | GFP | Caudate and SN | MPTP i.m. (2 mg/kg cumulative dose; administered over 5-day period) | 2 | Azathioprine, CsA and prednisolone | None | None | None | 6 weeks |
| Hallett et al. (2015) | Cynomolgus (M. fascicul ris) | Cynomolgus; autograft | iPSC-derived DAergic progenitors (Cooper et al. 2010 protocol) | None | Unilateral postcommissural putamen; 4 tracts total | MPTP i.v. (0.15–0.3 mg/kg) every 1–2 weeks | 1 | None | None | Clinical rating, activity monitoring, FMS | [11C]CFT | 2 years |
| Cynomolgus (M. fascicularis) | Cynomolgus; autograft | iPSC-derived DAergic progenitors (Sundberg et al. 2013 protocol) | None | Unilateral postcommissural putamen; 4 tracts total | MPTP i.v. (0.15–0.3 mg/kg) every 1–2 weeks | 2 | None | None | Clinical rating, activity monitoring, FMS | [11C]CFT | 2 years | |
| Cynomolgus (M. fascicularis) | Cynomolgus; allograft | ESC-derived DAergic progenitors (Sanchez-Pernaute et al. 2005 protocol) | None | Unilateral putamen | MPTP i.v. (0.15–0.3 mg/kg) every 1–2 weeks | 3 | None | None | Clinical rating, activity monitoring, FMS | [11C]CFT | 1 year | |
| Cynomolgus (M. fascicularis) | N/A | N/A | N/A | N/A | MPTP i.v. (0.15–0.3 mg/kg) every 1–2 weeks | 4 | None | None | Clinical rating, activity monitoring, FMS | [11C]CFT | 2 years | |
| Wang et al. (2015) | Cynomolgus (M. fascicularis) | Cynomolgus; autograft | iPSC-derived DAergic progenitors | GFP and Feridex IV | Unilateral (ipsi-MPTP) rostral, intermediate and caudal caudate and putamen, and SN; 7 tracts total | MPTP ICA (3 mg) | 1 | None | None | Clinical rating | None | 6 months |
| Cynomolgus (M. fascicularis) | N/A | Vehicle | N/A | Unilateral (ipsi-MPTP) rostral, intermediate and caudal caudate and putamen, and SN; 7 tracts total | MPTP ICA (3 mg) | 3 | None | None | Clinical rating | None | 6 months |
Immunosup immunosuppression, PET positron emission tomography, ESC embryonic stem cell, iPSC induced pluripotent stem cell, DAergic dopaminergic, BrdU 5-Bromo-2′-deoxyuriding, MPTP 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, L-DOPA L-3,4-dihydroxyphenylalanine, ipsi ipsilateral, i.v. intravenous, ICA intracarotid artery, mg milligram, kg kilogram, CsA Cyclosporine A, GFP green fluorescent protein, n.r. not reported, N/A not applicable, FMS fine motor skills, SN substantia nigra, [18 F]DOPA 6-[18 F]fluoro-l-3,4-dihydroxyphenylalanineresentatio, [11 C]DTBZ [11 C]dihydrotetrabenazine, [11 C]PE2I (E)-N-(3-iodoprop-2-enyl)-2β-carbo[11 C]methoxy-3β-(4-methylphenyl)nortropane, [18 F]FLT 3′-deoxy-3′3[18 F]fluorothymidine