A Clonal Line of Mesencephalic Progenitor Cells Converted to Dopamine Neurons by Hematopoietic Cytokines: A Source of Cells for Transplantation in Parkinson's Disease

Carvey, Paul M.; Ling, Zaodung; Sortwell, Caryl E.; Pitzer, Mark R.; McGuire, Susan O.; Storch, Alexander; Collier, Timothy J.

doi:10.1006/exnr.2001.7735

Cited by 134 publications

(83 citation statements)

References 35 publications

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“…Forebrain tissue was dissected and pulled from C57/Bl6 E.16 mouse embryos and expanded in culture as described previously [5,17]. Pregnant females were euthanized according to NIH guidelines and the approval of the local animal care committee.…”

Section: Neurosphere Isolation and Propagationmentioning

confidence: 99%

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Cryopreservation Does Not Affect Proliferation and Multipotency of Murine Neural Precursor Cells

2005

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Stem cell research offers unique opportunities for developing new medical therapies for devastating diseases and a new way to explore fundamental questions of biology. Establishing an efficient freezing protocol for neural precursor cells (NPCs) is of great importance for advances in cell-based therapies. We used fluorescence-activated cell sorter-based cell death/survival analysis and Western blot analysis of proliferation markers (proliferating cell nuclear antigen) and prosurvival proteins (Bcl-2) to study the effect of a variety of cryoprotective agents on fetal mouse forebrain NPCs. Neurospheres frozen at -70ºC or in liquid nitrogen in a ratecontrolled manner and thawed after 5 days retained viability of 60%-70% measured 24 hours after thawing. However, 1 week after thawing, viability dropped to 50%-60%. Using a clonogenic sphere formation assay, we showed that recovery rate of frozen NPCs was approximately 26% and did not significantly differ between dimethyl sulfoxide (DMSO)-and glycerol-supplemented samples. Application of the caspase inhibitor zVAD-fmk during freezing or in the first week after thawing resulted in protection of cryopreserved neurospheres after thawing but not during the freezing process, indicating that apoptosis limits recovery of NPCs. Cell survival was not reduced in cells that were enzymatically separated before cryopreservation. Optimal protection of NPCs was achieved when 10% DMSO alone or in a combination with 10% fetal calf serum (FCS) was used. However, 10% glycerol alone was equally effective. Using these protocols, NPCs retained their multipotency and differentiated into both glial (GFAP-positive) and neuronal (Tuj1-positive) cells. Percentage of Tuj1-positive cells in 5% and 10% DMSO, in 10% DMSO + 10% FCS, and in 10% glycerol remained at the same level as before freezing and varied from 5%-7%. We conclude that cryopreservation (up to 1 month at -70°C and up to 1 year in liquid nitrogen) does not markedly alter the rate of proliferation and multipotency of murine neural precursor cells. Stem Cells

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Section: Neurosphere Isolation and Propagationmentioning

confidence: 99%

“…Therefore, development of appropriate cryopreservation techniques is required. Cryopreservation of murine neural precursor cells (NPCs) has been done using dimethyl sulfoxide (DMSO) (Me 2 SO) [5,6]. However, the role of different cryoprotectants in the preservation of murine NPCs has not been studied in detail.…”

Section: Introductionmentioning

confidence: 99%

Cryopreservation Does Not Affect Proliferation and Multipotency of Murine Neural Precursor Cells

2005

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“…Other substances such as cytokines (i.e. interleukin-1β and interleukin-11) [46,56], and glial neurotrophic factors (GDNF) (i.e. neurturin; NTN) [57] may also be able to modulate and increase NSC differentiation towards a DA-ergic phenotype.…”

Section: Insciences Journal | Stem Cellsmentioning

confidence: 99%

The Use of Stem Cells in the Treatment of Parkinsons Disease

Su¹,

Loane²,

Politis³

2011

Insciences J.

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Abstract:Parkinson's disease (PD) is a degenerative neurological disorder characterized by the cardinal motor features of tremor, bradykinesia and rigidity. It is associated with the extended loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) resulting in a severe deficiency of DA in the striatum required for motor control. There is currently no cure for PD and the majority of treatments available aim to reverse dopamine deficiency and the relief of the symptoms. Based on promising findings from early trials, the transplantation of stem cells or stem cell derived progenitors has raised the possibility of using cell-based therapy to replace lost cells in the diseased brain. Embryonic stem cells (ESCs) are highly expandable and pluripotent cells that have the ability to differentiate into all cell types of the human body, including nervous system tissues, meaning that they have the potential to offer a lasting treatment for PD and other neurological diseases. However, possible issues with safety and ethics associated with the use of undifferentiated ESCs in humans have meant that alternative sources of transplantable cells has to be considered. Additionally, another approach is the stimulation of brain repair by endogenous stem cells via external manipulation.In this review, recent advances in stem cell research in PD will be discussed, giving an overview of the various strategies including the use of different stem cell populations for cell replacement and the possible modulation of endogenous stem cells that have the potential to provide effective cell-based therapy in future.

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“…This finding may be related to the level of maturity of the tissue at the time of culture, given that mitogenic expansion has been shown to reduce the potential for fetal ventral mesencephalonderived precursor cells to differentiate into dopaminergic neurons. 17 Differentiation of HNPCs into dopaminergic cells may require exposure to additional exogenous factors in culture 15,51,66,86,93,97 or genetic manipulation 45,46 prior to transplantation. The differentiation of HNPCs into other neurochemical phenotypes, such as a GABAergic phenotype, already has been demonstrated.…”

Section: Differentiation Of Hnpcsmentioning

confidence: 99%

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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A Clonal Line of Mesencephalic Progenitor Cells Converted to Dopamine Neurons by Hematopoietic Cytokines: A Source of Cells for Transplantation in Parkinson's Disease

Cited by 134 publications

References 35 publications

Cryopreservation Does Not Affect Proliferation and Multipotency of Murine Neural Precursor Cells

Cryopreservation Does Not Affect Proliferation and Multipotency of Murine Neural Precursor Cells

The Use of Stem Cells in the Treatment of Parkinsons Disease

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

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