Using iPS Cells toward the Understanding of Parkinson’s Disease

Torrent, Roger; Rigotti, Francesca; Dell’Era, Patrizia; Memo, Maurizio; Raya, Ángel; Consiglio, Antonella

doi:10.3390/jcm4040548

Cited by 50 publications

(43 citation statements)

References 73 publications

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“…Observations from other neurological disorders, such as Alzheimer's (62) and Parkinson's disease (63), show a similar trend as what we have observed in ALS. A very elegant recent study (64) has provided important information that might explain why iPSC-derived neurons and glia might display mild signs of pathology (39,50,54,47).…”

Section: The Promises and Limitations Of Cell Reprogrammingsupporting

confidence: 75%

New In Vitro Models to Study Amyotrophic Lateral Sclerosis

Myszczynska

Ferraiuolo

2016

Brain Pathology

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Amyotrophic Lateral Sclerosis (ALS) is a complex multifactorial disorder, characterized by motor neuron loss with involvement of several other cell types, including astrocytes, oligodendrocytes and microglia. Studies in vivo and in in vitro models have highlighted that the contribution of nonneuronal cells to the disease is a primary event and ALS pathogenesis is driven by both cell-autonomous and non-cell autonomous mechanisms. The advancements in genetics and in vitro modeling of the past 10 years have dramatically changed the way we investigate the pathogenic mechanisms involved in ALS. The identification of mutations in transactive response DNA-binding protein gene (TARDBP), fused in sarcoma (FUS) and, more recently, a GGGGCC-hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9ORF72) and their link with familial ALS have provided new avenues of investigation and hypotheses on the pathophysiology of this devastating disease. In the same years, from 2007 to present, in vitro technologies to model neurological disorders have also undergone impressive developments. The advent of induced pluripotent stem cells (iPSCs) gave the field of ALS the opportunity to finally model in vitro not only familial, but also the larger part of ALS cases affected by sporadic disease. Since 2008, when the first human iPS-derived motor neurons from patients were cultured in a petri dish, several different techniques have been developed to produce iPSC lines through genetic reprogramming and multiple direct conversion methods have been optimised. In this review we will give an overview of how human in vitro models have been used so far, what discoveries they have led to since 2007, and how the recent advances in technology combined with the genetic discoveries, have tremendously widened the horizon of ALS research.

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Section: The Promises and Limitations Of Cell Reprogrammingsupporting

confidence: 75%

New In Vitro Models to Study Amyotrophic Lateral Sclerosis

Myszczynska

Ferraiuolo

2016

Brain Pathology

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“…PD is the second most popular age‐related progressive neurodegenerative disorder, which is primarily characterized by a selective loss of DA neurons and α‐synuclein (α‐syn) dysfunction . Neuronal loss is related to intracytoplasmic inclusions, which are called Lewy bodies and Lewy neurites . The neuronal protein, α‐syn, is the main part of the Lewy bodies and Lewy neurites .…”

Section: Supportive Materials In the Disease Modeling Of Neurologicalmentioning

confidence: 99%

“…Neuronal loss is related to intracytoplasmic inclusions, which are called Lewy bodies and Lewy neurites . The neuronal protein, α‐syn, is the main part of the Lewy bodies and Lewy neurites . Many PD cases are sporadic.…”

Section: Supportive Materials In the Disease Modeling Of Neurologicalmentioning

confidence: 99%

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Materials for Neural Differentiation, Trans‐Differentiation, and Modeling of Neurological Disease

et al. 2018

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Neuron regeneration from pluripotent stem cells (PSCs) differentiation or somatic cells trans-differentiation is a promising approach for cell replacement in neurodegenerative diseases and provides a powerful tool for investigating neural development, modeling neurological diseases, and uncovering the mechanisms that underlie diseases. Advancing the materials that are applied in neural differentiation and trans-differentiation promotes the safety, efficiency, and efficacy of neuron regeneration. In the neural differentiation process, matrix materials, either natural or synthetic, not only provide a structural and biochemical support for the monolayer or three-dimensional (3D) cultured cells but also assist in cell adhesion and cell-to-cell communication. They play important roles in directing the differentiation of PSCs into neural cells and modeling neurological diseases. For the trans-differentiation of neural cells, several materials have been used to make the conversion feasible for future therapy. Here, the most current applications of materials for neural differentiation for PSCs, neuronal trans-differentiation, and neurological disease modeling is summarized and discussed.

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“…With the advent of human induced pluripotent stem (hiPS) cells, human stem cell-derived models for neurodegenerative diseases are available, which have the potential to significantly add to the insights gained by non-human in vivo and in vitro research models [28][29][30][31][32]. With regard to PD, hiPS cell-derived DA neurons featuring the genetics of healthy donors and patients provide the opportunity to invesitgate disease-related pathomechanisms in a yet unexploited way.…”

Section: Introductionmentioning

confidence: 99%

Refinement of a neuronal differentiation protocol predominantly yields human iPS cell-derived dopaminergic neurons for the investigation of neurodegenerative pathomechanisms in vitro

Martí

Nürnberg

Horschitz

et al. 2017

JCB

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Abstract. BACKGROUND:Major pathomechanisms underlying neurodegenerative diseases, such as Parkinson's Disease, are still not well understood. Induced human pluripotent and rodent embryonic stem cells provide powerful disease models to address neurodegeneration-inducing pathomechanisms on a molecular and cellular level. OBJECTIVE: Our aim is to establish a refined protocol to generate healthy and patient donor stem cell-derived dopaminergic neurons to investigate neurodegenerative events in vitro. METHODS: Human healthy donor-and patient-derived induced pluripotent stem cells were differentiated into stable dopaminergic progenitor cell lines and further differentiated into dopaminergic neurons. Induced pluripotent stem cells, neuronal progenitors and terminally differentiated neurons were characterized by confocal laser microscopy-based immunofluorescence analysis, live cell imaging demonstrating dopamine transporter-specific uptake of a fluorescent substrate and transcriptome analysis. RESULTS: Based on our immunofluorescence analysis, dopaminergic differentiation approaches predominantly yield dopaminergic neurons and GFAP-expressing glial cells. We detected a small partition of GABAergic neurons, yet neither serotonergic nor glutamatergic neurons. Dopaminergic neurons were successfully stained for pre-and postsynaptic and mitochondrial markers. Live cell imaging experiments verified dopamine transporter-dependent uptake of the fluorescent monoamine transporter substrate ASP+. CONCLUSION: Human stem cell-derived dopaminergic neurons are a suitable cellular system for fluorescence-based experimental approaches to address neurodegenerative events in vitro.

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Using iPS Cells toward the Understanding of Parkinson’s Disease

Cited by 50 publications

References 73 publications

New In Vitro Models to Study Amyotrophic Lateral Sclerosis

New In Vitro Models to Study Amyotrophic Lateral Sclerosis

Materials for Neural Differentiation, Trans‐Differentiation, and Modeling of Neurological Disease

Refinement of a neuronal differentiation protocol predominantly yields human iPS cell-derived dopaminergic neurons for the investigation of neurodegenerative pathomechanisms in vitro

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