Table 1 Neural stem/progenitor cell transplantation in animal models of Huntington’s disease
Cells | Cell marker expression | Cell passage | Cell marker (visual) | Cell number and time of injection | Growth factor expression | Model/age | Time of analysis | Behavior/ striatal volume | Cell distribution/ survival | Cell differentiation | Cell migratory activity | Conclusions and references |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
Human fetal cortex stem cells (12 weeks post-conception) | Not specified | Neurospheres 12 weeks in culture | HN | 200,000 cells; striatum 1 week after QA | CNTF+, CNTF– | QA rat | 8 weeks post-graft | CNTF+ cells or CNTF– cells demonstrated significant improvement over the 8 weeks; increased striatal volume | Robust survival of HN and Ki-67-positive cells: striatum, GP, EPN, and SNpr | Co-localization of GFAP + HN in striatum only | CNTF– stronger migratory activity; GP, EPN, and SNpr | Striatal transplants of human fetal stem cells in HD rat QA model elicit behavioral and anatomical recovery [65] |
Immortalized huNSC lines from fetal telencephalon tissue | ABCG2+, nestin+, vimentin+ | No data | Lac Z | 1 × 106; right striatum 1 week prior to damage induction or 12 h after | BDNF secretion | 3-NP rat | 2 weeks post-graft | 1 week prior to damage induction: significantly improved motor performance and reduced damage to striatal neurons. 12 h after: no improvement in motor performance | Striatum; robust survival | Positive for beta-tubulin III, GFAP, calbindin, GAD | Limited migration to graft core in striatum | Improved motor functions and reduced cellular damage, neurotrophic support by secreted BDNF. Differentiation of huNSCs to GABAergic neurons, but not cholinergic or dopaminergic neurons [69] |
Immortalized huNSC line (15 weeks gestation) | Nestin+ | ~24 passages | Lac Z, BrdU | 5 × 106 cells; IV transplant; tail vein; 7 days post-QA | Not specified | QA rat | From 2 up to 8 weeks post-graft | Significantly greater striatal volume | Predominantly lesion side of hemisphere; additionally renal cortex, spleen and epithelium of bronchioles | BrdU+/GFAP+/NeuN+; BrdU+/parvalbumin–/DARRP-32–/calbindin– | 3 weeks after : X-gal + cells in striatum: in the parenchyma and around vessels | Intravenously transplanted NSCs migrate to the lesion site, reduce cellular damage, and induce functional recovery. Differentiate into neurons and glia, NTD [63] |
huNSCs: same as in Lee et al. [63]; 2n = 46, XX | Nestin+, vimentin+ | ~24 passages or more | Lac Z | 1 × 105 intraventricular; 10 × 105 IV | Not specified | QA rat | 3 weeks post-graft | No data | Predominantly lesion side of hemisphere | No data | From 2 to10 weeks X-gal + cells in striatum: in the parenchyma and around vessels | NSCs migrate into the striatum, from both ventricle or systemic circulation, NTD [64] |
Immortalized mNSCs: MHP36 cells | Not specified | Not specified | PKH26 | ~400,000 cells; striatum | Not specified | 3-NP rat | 14 weeks post-graft | No effect on striatal volume | Predominantly populated areas of damage | Endogenous glial differentiation; PKH26 cell differentiation into astrocytes and neurons | Graft in the region of neuronal loss and striatum, no migration | MRI. Partial recovery of learning in water maze. No effect on striatal volume. Implanted cells did not penetrate through the glial scar to reconstruct lost tissue [68] |
Allotransplant of striatal cells: a) neurospheres; b) cell suspension | Not specified | Neurospheres third to sixth passage | EGFP+ | 40,000 cells; striatum; 2, 7, and 14 days after QA | Endogenous BDNF expression stable before and after cell transplant | a,b) QA mice; c) R6/2 mice | 14 days and 3 months post-graft | Not specified | a) 2 days after QA: significant graft survival | a) GFAP+ up to 3 months | Better migration of the cells in R6/2 versus QA | a) Best survival: combination of early transplantation + neurospheres |
b) 7 and 14 days after QA: reduced graft survival | b) Undifferentiated | b) Astroglia and microglia activation in the striatum after injection of QA After 3 months the graft volume was reduced [62] | ||||||||||
c) 3 to 4 weeks survival time | ||||||||||||
Adult SVZ-derived rNPC | SOX2+ | Neurospheres; suspension; passage not specified | BrdU-labeled cells | ∼180,000 cells; striatum | Not specified | QA rat | 8 weeks post-graft | Reduce functional impairment | ∼12 % graft survival | GFAP+, NeuN+, DARPP-32+, GAD67+ | Migrated extensively; striatum | Neural progenitor cell transplantation reduces rotational asymmetry and impairment of spontaneous exploratory forelimb use [66] |
Embryonic LGE and MGE-derived rNSCs | Nestin+, GFAP+ | Passage 2 | PKH26, Hoechst, TOTO-3 | 100,000 cells; striatum | SCF | QA rat | 3 or 8 weeks post-graft | Not specified | 3 weeks | Undifferentiated | Striatum | SCF increased expression [61] |
Adult SVZ-derived rNPCs pretreated with LiCl | SOX2+ | Cultured in vitro 14 days before transplant | BrdU-labeled cells | ∼150,000 cells; striatum; 21 days after QA | Not specified | QA rat | 12 weeks post-graft | Acceleration of sensorimotor function recovery | Increased survival | GFAP+, NeuN+, DARPP-32+, GAD67+ | Migration in striatum | LiCl priming did not alter the maximal distribution of NPCs across the striatum, while augmenting transplant efficiency and accelerating sensorimotor function outcome in vivo [67] |