Human pluripotent stem cells as tools for neurodegenerative and neurodevelopmental disease modeling and drug discovery

Corti, Stefania; Faravelli, Irene; Cardano, Marina; Conti, Luciano

doi:10.1517/17460441.2015.1037737

Cited by 52 publications

(45 citation statements)

References 96 publications

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“…Human induced pluripotent stem cells (iPSCs) are increasingly used in model systems of neurological disorders (Sandoe and Eggan, 2013; Corti et al , 2015). They facilitate the study of human proteins in their normal cellular context, and, through the reprogramming of patient-derived samples, allow the impact of mutations to be investigated within a relevant polygenetic background.…”

Section: Introductionmentioning

confidence: 99%

Co-cultures with stem cell-derived human sensory neurons reveal regulators of peripheral myelination

Clark

Kaller

Galino

et al. 2017

Brain

101

112

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See Saporta and Shy (doi:) for a scientific commentary on this article.Clark et al. report that human sensory neurons derived from iPSCs can be myelinated by rat Schwann cells in culture. Such co-cultures develop features of mature myelinated fibres in a neuregulin-1 dependent manner. Antiganglioside antibodies associated with inflammatory peripheral neuropathies can both impede myelination and cause loss of established myelin.

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Section: Introductionmentioning

confidence: 99%

Co-cultures with stem cell-derived human sensory neurons reveal regulators of peripheral myelination

Clark

Kaller

Galino

et al. 2017

Brain

101

112

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“…The successful generation of iPSCs from patients' specific somatic cells, and differentiation to cortical neurons, have offered cell resources for disease modeling and potential cell transplantation therapy [32]. This revolutionary technology has already helped to advance our understanding of many diseases and inform mechanistically rationalized therapies, which are desperately needed in this arena [6, 33]…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, human iPSCs can lead to the identification and optimization of potential drugs and thus move forward new pharmacological therapies for a wide range of neurodegenerative and neurodevelopmental conditions [32]. Critical to this field is the consistent manufacturing of differentiated neurons from iPSCs.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of inter-batch differences in stem-cell derived neurons

et al. 2016

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Differentiated cells retain the genetic information of the donor but the extent to which phenotypic differences between donors or batches of differentiated cells are explained by variation introduced during the differentiation process is not fully understood. In this study, we evaluated four separate batches of commercially available neurons originating from the same iPSCs to investigate whether the differentiation process used in manufacturing iPSCs to neurons affected genome-wide gene expression, modified cytosines, or neuronal sensitivity to drugs. No significant changes in gene expression, as measured by RNA-Seq, or cytosine modification levels, as measured by the Illumina 450K arrays, were observed between batches relative to changes over time. As expected, neurotoxic chemotherapeutics affected neuronal outgrowth, but no inter-batch differences were observed in sensitivity to paclitaxel, vincristine and cisplatin. As a testament to the utility of the model for studies of neuropathy, we observed that genes involved in neuropathy had relatively higher expression levels in these samples across different time points. Our results suggest that the process used to differentiate iPSCs into neurons is consistent, resulting in minimal intra-individual variability across batches. Therefore, this model is reasonable for studies of human neuropathy, druggable targets to prevent neuropathy, and other neurological diseases.

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“…Most importantly, animal-free basic biomedical research possibilities also have been transformed dramatically. The most important new trends comprise the advent of human stem cell technology (Corti et al, 2015;Singh et al, 2015;Schadt et al, 2014;Giri and Bader, 2015;Kim et al, 2014;Lancaster and Knoblich, 2014;Karakikes et al, 2014;Inoue et al, 2014;Ko and Gelb, 2014), the option to introduce defined genetic changes into such cells (Li et al, 2014), and the construction of microphysiological systems based on human cells (Materne et al, 2015;Fabre et al, 2014;Sung et al, 2014;Hartman et al, 2014;Marx et al, 2012;Andersen et al, 2014;Hartung, 2014).…”

Section: Altered Scientific Situationmentioning

confidence: 99%