Human neural stem cell transplantation in the MPTP-lesioned mouse

Liker, Mark A.; Petzinger, Giselle M.; Nixon, Kerry; McNeill, Thomas H.; Jakowec, Michael W.

doi:10.1016/s0006-8993(03)02337-0

Cited by 33 publications

(15 citation statements)

References 62 publications

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“…Thus, engrafted HNPs did not express TH or other neurotransmitters. This is consistent cells appeared morphologically and biochemically more developed than NSPs, neither cell type differentiated with previous reports of human NSPs, where the un- prompted expression of TH was only rarely (41) or tran-addition to species. First, mouse progenitor cells were derived from a line originally isolated from the newborn siently (51) seen in engrafted HNPs.…”

Section: Studies Of Hnps In Culturesupporting

confidence: 92%

Studies on the Differentiation of Dopaminergic Traits in Human Neural Progenitor Cells in Vitro and in Vivo

et al. 2004

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The development of cell replacement therapies for the treatment of neurodegenerative disorders such as Parkinson's disease (PD) may depend upon the successful differentiation of human neural stem/progenitor cells into dopamine (DA) neurons. We show here that primary human neural progenitors (HNPs) can be expanded and maintained in culture both as neurospheres (NSPs) and attached monolayers where they develop into neurons and glia. When transplanted into the 6-hydroxydopamine-lesioned rat striatum, undifferentiated NSPs survive longer (60% graft survival at 8-16 weeks vs. 30% graft survival at 8-13 weeks) and migrate farther than their attached counterparts. While both NSP and attached cells continue to express neuronal traits after transplantation, the spontaneous expression of differentiated transmitter-related traits is not observed in either cell type. However, following predifferentiation in culture using a previously described cocktail of reagents, approximately 25% of HNPs can permanently express the DA enzyme tyrosine hydroxylase (TH), even following replating and removal of the DA differentiation cocktail. When these predifferentiated HNPs are transplanted into the brain, however, TH staining is not observed, either because expression is lost or TH-expressing cells preferentially die. Consistent with the latter view is a decrease in total cell survival and migration, and an enhanced glial response in these grafts. In contrast, we found that the overall survival of HNPs is improved when cells engraft near blood vessels or CSF compartments or when they are placed into an intact unlesioned brain, suggesting that there are factors, as yet unidentified, that can better support the development of engrafted HNPs.

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Section: Studies Of Hnps In Culturesupporting

confidence: 92%

Studies on the Differentiation of Dopaminergic Traits in Human Neural Progenitor Cells in Vitro and in Vivo

et al. 2004

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“…Migration appeared to be nondirected, with dispersion of HNPCs away from the graft core, which is consistent with other HNPC transplantation studies in which cells were observed to migrate, particularly in white matter structures. 18,23,54,58,95,106 Transplanted precursor cells have been reported to migrate in a directed manner, toward sites of injury, for example; 11,59,99 however, this type of movement was not the case in the present study, given that no HNPCs transplanted in the striatum were observed in the lesioned SN. Our findings also contrast with those indicating that HNPC migration was unrelated to the amount of time in culture.…”

Section: Migration Of Hnpcscontrasting

confidence: 62%

Survival, differentiation, and migration of bioreactor-expanded human neural precursor cells in a model of Parkinson disease in rats

Mukhida

Baghbaderani

Hong

et al. 2008

FOC

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Object Fetal tissue transplantation for Parkinson disease (PD) has demonstrated promising results in experimental and clinical studies. However, the widespread clinical application of this therapeutic approach is limited by a lack of fetal tissue. Human neural precursor cells (HNPCs) are attractive candidates for transplantation because of their long-term proliferation activity. Furthermore, these cells can be reproducibly expanded in a standardized fashion in suspension bioreactors. In this study the authors sought to determine whether the survival, differentiation, and migration of HNPCs after transplantation depended on the region of precursor cell origin, intracerebral site of transplantation, and duration of their expansion. Methods Human neural precursor cells were isolated from the telencephalon, brainstem, ventral mesencephalon, and spinal cord of human fetuses 8–10 weeks of gestational age, and their differentiation potential characterized in vitro. After expansion in suspension bioreactors, the HNPCs were transplanted into the striatum and substantia nigra of parkinsonian rats. Histological analyses were performed 7 weeks posttransplantation. Results The HNPCs isolated from various regions of the neuraxis demonstrated diverse propensities to differentiate into astrocytes and neurons and could all successfully expand under standardized conditions in suspension bioreactors. At 7 weeks posttransplantation, survival and migration were significantly greater for HNPCs obtained from the more rostral brain regions. The HNPCs differentiated predominantly into astrocytes after transplantation into the striatum or substantia nigra regions, and thus no behavioral improvement was observed. Conclusions Understanding the regional differences in HNPC properties is prerequisite to their application for PD cell restoration strategies.

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“…NSCs can participate in repair of damage and may be useful in the treatment of degenerative brain conditions (11). In models of Parkinson's disease, NSCs have been observed to integrate and survive for extended periods of time (12), and to rescue and prevent the degeneration of endogenous dopaminergic neurons (13).…”

Section: Viability-dependent Promoting Action Of Adult Neural Precursmentioning

confidence: 99%

Viability-Dependent Promoting Action of Adult Neural Precursors in Spinal Cord Injury

Bottai

Madaschi

Giulio

et al. 2008

Mol Med

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The aim of the study was the assessment of the effects of adult neural stem cell (NSC) transplantation in a mouse model of spinal cord injury (SCI). The contusion injury was performed by means of the Infinite Horizon Device to allow the generation of reproducible traumatic lesion to the cord. We administered green fluorescent-labeled (GFP-)NSCs either by intravenous (i.v.) injection or by direct transplantation into the spinal cord (intraspinal route). We report that NSCs significantly improved recovery of hind limb function and greatly attenuated secondary degeneration. The i.v. route of NSC administration yielded better recovery than the intraspinal route of administration. About 2% of total i.v.-administered NSCs homed to the spinal cord injury site, and survived almost undifferentiated; thus the positive effect of NSC treatment cannot be ascribed to damaged tissue substitution. The NSCs homing to the injury site triggered, within 48 h, a large increase of the expression of neurotrophic factors and chemokines. One wk after transplantation, exogenous GFP-NSCs still retained their proliferation potential and produced neurospheres when recovered from the lesion site and cultured in vitro. At a later time, GFP-NSC were phagocytated by macrophages. We suggest that the process of triggering the recovery of function might be strongly related to the viability of GFP-NSC, still capable ex vivo of producing neurospheres, and their ability to modify the lesion environment in a positive fashion.

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Human neural stem cell transplantation in the MPTP-lesioned mouse

Cited by 33 publications

References 62 publications

Studies on the Differentiation of Dopaminergic Traits in Human Neural Progenitor Cells in Vitro and in Vivo

Studies on the Differentiation of Dopaminergic Traits in Human Neural Progenitor Cells in Vitro and in Vivo

Survival, differentiation, and migration of bioreactor-expanded human neural precursor cells in a model of Parkinson disease in rats

Viability-Dependent Promoting Action of Adult Neural Precursors in Spinal Cord Injury

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