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Table 1 Neural stem/progenitor cell transplantation in animal models of Huntington’s disease

From: Neural and mesenchymal stem cells in animal models of Huntington’s disease: past experiences and future challenges

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]
  1. 3-NP 3-nitropropionic acid, BDNF brain-derived neurotrophic factor, BrdU bromodeoxyuridine, CNTF ciliary neurotrophic factor, DARPP-32 dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa, EGFP enhanced green fluorescent protein, EPN entopeduncular, GABA gamma aminobutyric acid, GAD glutamate decarboxylase, GFAP glial fibrillary acidic protein, GP globus pallidus, HD Huntington’s disease, HN human-specific marker to nuclear antigen, huNSC human neuronal stem cell, IV intravenous, LacZ beta galactosidase, LGE lateral ganglionic eminence, MGE medial ganglionic eminence, mNSC murine neuronal stem cell, MRI magnetic resonance imaging, NPC neuronal progenitor cells, NSC neuronal stem cell, NTD no tumorigenesis detected, QA quinolinic acid, rNPC rat neuronal progenitor cells, rNSC rat neuronal stem cell, SCF stem cell factor, SNpr substantia nigra pars reticulate, SVZ subventricular zone, X-gal 5-bromo-4-chloro-3-indolyl-β-D-galatopyranoside