Table 2.
Summary of grafting of human iPSC-derived DA neuron differentiated culture into PD rat model
| [Ref], source (protocol: stage of graft)/ graft site | Total cell number, [cell composition] | Functional recovery | Survival of grafts (W/M post grafting) | Characteristics of grafts of DA neuron differentiated culture | Neurite outgrowth & striatum reinnervation | Side effects |
|---|---|---|---|---|---|---|
| [61], hiPSC lines 2C6, SeV6 ((1) floor plate: d25 (12 days post withdrawal of CHIR); (2) MS5: 14 days post withdrawal of SHH & FGF8)/ CPu | 2.5 × 105 cells [(1): 18 % TH+/FOXA2+, 40 % NUUR1+/FOXA2+, 95 % LMX1A+/FOXA2+ (2): 30 % TH+, 20 % Nurr1+, low in FOXA2, LMX1A] |
(4.5 MPG) Amphetamine: (1): >100 % reduction Stepping test: (1): 30 % increase Cylinder test: (1): >10 % reduction (2): all tests n.s. |
(4.5 MPG) (1): 15,000 TH+/FOXA2+ cells; serotonergic and GABA-ergic neurons <1 % (2): Few TH+ neurons |
n.d. | TH+/NCAM+ fibres extended into striatum. | (2): Neural overgrowth in NOD-SCID IL2Rgc null mice |
| [75], hiPSC line 836B3 (floor plate, (1) d28, (2) d42 (withdrawal of purmorphamine, FGF8 at d7; CHIR99021 at day 12))/CPu | 4 × 105 cells (CORIN+ sorting at d12, or not) [(1): 70–75 % FOXA2+, 27.3 % NURR1+ cells, 2.1 % TH+ cells (2): 70–75 % FOXA2+, 19.9 % NURR1+ cells, 42.0 % TH+ cells] |
(16 WPG) Amphetamine: (1): 78 % reduction (2): n.s. |
(1) Sorted: 6747 TH+ cells; 2.5 % serotonin+ (1) Unsorted 3,4364 TH+ cells; 1.2 % serotonin+ (2) Sorted: 1900 TH+ cells (2) Unsorted 2000 TH+ cells. |
Co-expression of TH, FOXA2, NURR1 and PITX3; 50 % of the TH+ cells co-expressed GIRK2. | More neurite outgrowth in the grafts derived from the day 12 CORIN+ sorted cells | Large graft size of unsorted grafts |
| [76], Lenti, retro, protein hiPSCs, hESCs (MS5: (1) NPCs P1-P2; (2) NPCs P4; (3) day 5 post withdraw of SHH & FGF8)/CPu |
(1): 7.5 × 105 cells (2): 3 × 105 cells (3): 3 × 105 cells [(3): 5 % GFAP+, 60–70%TUJ1+, 35–45 % TH+ in TUJ1+ cells, 5–10 % serotonin+, a few GABAergic and glutamatergic neuronal cells] |
(8 WPG) Amphetamine (1): 76.43 % reduction (2): 47.54 % reduction (3): 0 % reduction |
(1) 54,418 TH+ cells (half size of striatum) (2) 26,882 TH+ cells (3) No TH+ cells |
Co-expression of TH, TuJ1 and VMAT2; Nurr1 and EN1 Oct4+ in some lentivirus-based hiPSCs-derived neurons |
n.d. | Tumor formation |
| [82], PDiPSC (MS5: day 42, 5 days post withdrawal of SHH & FGF8)/CPu |
(1): 4 × 105 unsorted cells (2): 4 × 105 NCAM+ sorted cells 5–10 % TH+ cells |
(16WPG) Amphetamine: (1) 56 % reduction (2) 52 % reduction Apomorphine: (1) 37 % reduction (2) 0 % |
(1) 4890 TH+ cells (2) 350 TH+ cells |
(12WPG) 53.4 % DA neurons GIRK2+; 6.6 % DA neurons calbindin+ 4.7 % forebrain DA neurons 5.8 % hypothalamic DA neurons 0.09 ± 0.02 % Ki-67+ 83.1 ± 8.2 % hNCAM+ No SSEA-4- nor Oct4+; no ubiquitin + and α-synuclein + inclusion bodies |
A few TH+ fibers extended towards the striatum | n.d. |
Abbreviations: CPu Caudate-putamen, WPG Weeks post grafting, MPG Months post grafting, n.s. No significant improvement, hiPSC Human iPSC, PDiPSC PD patient iPSC, n.d. Not determined/not described