Towards stem cell based therapies for Parkinson's disease

Parmar, Malin

doi:10.1242/dev.156117

Cited by 59 publications

(38 citation statements)

References 29 publications

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“…In adults, NSCs are localized in the sub-ventricular zone (SVZ) and hippocampus [21,22]. As with drug therapy, many studies have suggested that NSC transplantation improves cognitive behaviour in animal models of AD [23], Parkinson's disease [24,25] Huntington's disease [26,27], amyotrophic lateral sclerosis [28] and other neurodegenerative diseases. After transplantation, NSCs differentiate into neurons and/or glial cells and release trophic factors.…”

Section: Neural Stem Cellsmentioning

confidence: 99%

Effects of neural stem cell transplantation in Alzheimer’s disease models

et al. 2020

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Currently there are no therapies for treating Alzheimer's disease (AD) that can effectively halt disease progression. Existing drugs such as acetylcholinesterase inhibitors or NMDA receptor antagonists offers only symptomatic benefit. More recently, transplantation of neural stem cells (NSCs) to treat neurodegenerative diseases, including AD, has been investigated as a new therapeutic approach. Transplanted cells have the potential to replace damaged neural circuitry and secrete neurotrophic factors to counter symptomatic deterioration or to alter lesion protein levels. However, since there are animal models that can recapitulate AD in its entirety, it is challenging to precisely characterize the positive effects of transplanting NSCs. In the present review, we discuss the types of mouse modeling system that are available and the effect in each model after human-derived NSC (hNSC) or murine-derived NSC (mNSC) transplantation. Taken together, results from studies involving NSC transplantation in AD models indicate that this strategy could serve as a new therapeutic approach.

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Section: Neural Stem Cellsmentioning

confidence: 99%

Effects of neural stem cell transplantation in Alzheimer’s disease models

et al. 2020

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“…There are several classes of DA neurons in the vertebrate CNS, including those mediating motor functions in the midbrain and others controlling secretion of neuropeptides in the hypothalamus (Flames and Hobert 2011;Grattan 2015). There is considerable information about the specification of midbrain DA neurons due to their importance in Parkinson's disease (Flames and Hobert 2011;Kee et al 2017;Kirkeby et al 2017;Parmar 2018). Characterization of the molecular programs controlling differentiation of DA neurons is crucial for understanding this important neuronal cell type and developing stem cellbased therapies for DA deficiencies such as Parkinson's disease (Parmar 2018).…”

mentioning

confidence: 99%

Regulatory cocktail for dopaminergic neurons in a protovertebrate identified by whole-embryo single-cell transcriptomics

Horie

Chen

et al. 2018

Genes Dev.

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The CNS of the protovertebrate contains a single cluster of dopaminergic (DA) neurons, the coronet cells, which have been likened to the hypothalamus of vertebrates. Whole-embryo single-cell RNA sequencing (RNA-seq) assays identified as the most strongly expressed cell-specific transcription factor (TF) in DA/coronet cells. Knockdown of activity results in their loss, while misexpression results in the appearance of supernumerary DA/coronet cells. Photoreceptor cells and ependymal cells are the most susceptible to transformation, and both cell types express high levels of Coexpression of both and caused the wholesale transformation of the entire CNS into DA/coronet cells. We therefore suggest that the reiterative use of functional manipulations and single-cell RNA-seq assays is an effective means for the identification of regulatory cocktails underlying the specification of specific cell identities.

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“…Cell therapy involves the manufacturing and use of cells to replace dead or deficient cells 5 and is a promising avenue to treat PD. [6][7][8] This is exemplified by the clinical trials that will begin in 2019-2020 in the United States, 9 Europe, 10 China, 11 and Japan. 12 One major concern with cell therapy is the potential for heterogeneity of cells used in transplantation 13 reflected by the variation in success of the therapy when attempted with fetal cells, where some PD patients eliminated the need for L-dopa therapy, 14 whereas others suffered graft rejection, graft-induced dyskinesia, 15 or unsuccessful grafting and/or no DA production as measured postmortem or via Positron Emission Tomography/Magnetic Resonance Imaging studies.…”

Section: Introductionmentioning

confidence: 99%

Stimulation of L-type calcium channels increases tyrosine hydroxylase and dopamine in ventral midbrain cells induced from somatic cells

Jefri

Bell

Peng

et al. 2020

Stem Cells Translational Medicine

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Making high-quality dopamine (DA)-producing cells for basic biological or small molecule screening studies is critical for the development of novel therapeutics for disorders of the ventral midbrain. Currently, many ventral midbrain assays have low signal-to-noise ratio due to low levels of cellular DA and the rate-limiting enzyme of DA synthesis, tyrosine hydroxylase (TH), hampering discovery efforts. Using intensively characterized ventral midbrain cells derived from human skin, which demonstrate calcium pacemaking activity and classical electrophysiological properties, we show that an L-type calcium agonist can significantly increase TH protein levels and DA content and release. Live calcium imaging suggests that it is the immediate influx of calcium occurring simultaneously in all cells that drives this effect. Genome-wide expression profiling suggests that L-type calcium channel stimulation has a significant effect on specific genes related to DA synthesis and affects expression of L-type calcium receptor subunits from the CACNA1 and CACNA2D families. Together, our findings provide an advance in the ability to increase DA and TH levels to improve the accuracy of disease modeling and small molecule screening for disorders of the ventral midbrain, including Parkinson's disease. K E Y W O R D S cell biology, induced pluripotent stem cells (iPSCs), nervous system, neural differentiation, neural induction Malvin Jefri and Scott Bell are co-first authors.

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Towards stem cell based therapies for Parkinson's disease

Cited by 59 publications

References 29 publications

Effects of neural stem cell transplantation in Alzheimer’s disease models

Effects of neural stem cell transplantation in Alzheimer’s disease models

Regulatory cocktail for dopaminergic neurons in a protovertebrate identified by whole-embryo single-cell transcriptomics

Stimulation of L-type calcium channels increases tyrosine hydroxylase and dopamine in ventral midbrain cells induced from somatic cells

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