Large-scale screening using familial dysautonomia induced pluripotent stem cells identifies compounds that rescue IKBKAP expression

Lee, Gabsang; Ramirez, Christina N.; Kim, Hyesoo; Zeltner, Nadja; Liu, Becky; Radu, Constantin; Bhinder, Bhavneet; Kim, Yong Jun; Choi, In Young; Mukherjee-Clavin, Bipasha; Djaballah, Hakim; Studer, Lorenz

doi:10.1038/nbt.2435

Cited by 211 publications

(166 citation statements)

References 21 publications

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“…using patient-specific iPS cells, refined methods of differentiating and isolating cells for target tissue is indispensable. Although recently there has been a great deal of research into patient-specific iPS cells [39][40][41][42][43][44][45][46][47][48][49][50][51][52], research into their use in the vasculature and endocrine organs is still rare [53]. We are now investigating the pathogenesis of several inherited vascular disorders with collaborators.…”

Section: Acknowledgementmentioning

confidence: 99%

Vascular research using human pluripotent stem cells and humoral factors [Review]

Sone

Nakao

2013

Endocr J

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Abstract. Embryonic stem (ES) cells are pluripotent cells collected from the inner cell mass of blastocysts. Induced pluripotent stem cells exhibit characteristics and pluripotency similar to ES cells, even though they were generated from adult somatic cells. We have been investigating the vascular differentiation kinetics of human pluripotent stem cells (PSCs) and their application to human vascular research and clinical medicine. In this review, we present an overview of recent vascular research using human PSCs, focusing on the role of humoral factors and their receptors. We also discuss possible future application of human PSCs to translational research on human vascular disorders.

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Section: Acknowledgementmentioning

confidence: 99%

Vascular research using human pluripotent stem cells and humoral factors [Review]

Sone

Nakao

2013

Endocr J

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“…In 2012, for example, neural stem cells made from people with a nerve-cell-development disease were used to screen nearly 7,000 small molecules and identify a potential drug for the condition 13 . And this year, a team reported 14 generating sensory neurons from iPS cells made from people with an inherited pain disorder.…”

Section: Cellular Improvementsmentioning

confidence: 99%

How iPS cells changed the world

Scudellari¹

2016

Nature

120

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“…It is perhaps worthwhile for industry to evaluate an iPSCbased approach in their drug discovery process for screening large compound libraries given recent documented successes [22][23][24][25][26]. Zhao et al provide a noteworthy example supporting iPSC-based screens for novel drug discovery [27].…”

Section: Modeling Disease Using Human Cells In General and Psc-derivementioning

confidence: 99%

Induced Pluripotent Stem Cell Models to Enable In Vitro Models for Screening in the Central Nervous System

Hunsberger

Efthymiou

Malik

et al. 2015

Stem Cells and Development

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There is great need to develop more predictive drug discovery tools to identify new therapies to treat diseases of the central nervous system (CNS). Current nonpluripotent stem cell-based models often utilize non-CNS immortalized cell lines and do not enable the development of personalized models of disease. In this review, we discuss why in vitro models are necessary for translational research and outline the unique advantages of induced pluripotent stem cell (iPSC)-based models over those of current systems. We suggest that iPSC-based models can be patient specific and isogenic lines can be differentiated into many neural cell types for detailed comparisons. iPSC-derived cells can be combined to form small organoids, or large panels of lines can be developed that enable new forms of analysis. iPSC and embryonic stem cell-derived cells can be readily engineered to develop reporters for lineage studies or mechanism of action experiments further extending the utility of iPSC-based systems. We conclude by describing novel technologies that include strategies for the development of diversity panels, novel genomic engineering tools, new three-dimensional organoid systems, and modified high-content screens that may bring toxicology into the 21st century. The strategic integration of these technologies with the advantages of iPSC-derived cell technology, we believe, will be a paradigm shift for toxicology and drug discovery efforts.Disease Modeling D iseases of the central nervous system (CNS) affect a large number of people, but therapeutic intervention is hampered by the lack of useful models for many of these diseases. Current research on human subjects, particularly for drug discovery for CNS diseases, is severely (and appropriately) limited by ethical guidelines. Therefore, surrogate models are needed that share important anatomical, physiological, and genetic features to advance new treatments and therapies for CNS diseases [1].Developing rapid and effective therapies for CNS diseases requires the availability of in vitro models that accurately recapitulate disease phenotypes and predict patient treatment response. A proper model must be both sensitive and predictive while reflecting both normal and disease processes. Equally important, these models should enable the investigation of genetic and environmental risk factors contributing to diseases in a rapid and economical way. Currently used models often do not reflect a typical human response [2-4], despite efforts underway to better characterize these models and increase their preclinical value in predicting safety and efficacy in the clinic [5,6]. Therefore, there is a great need to develop disease-and patient-specific models from cells directly affected in CNS disorders. These cellbased models, we envision, could either replace or supplement current animal models and enable the efficient translation of basic research into the clinical setting. Limitations with current CNS modelsCurrently, drug discovery relies on the use of animalbased or cell-based models, ...

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Large-scale screening using familial dysautonomia induced pluripotent stem cells identifies compounds that rescue IKBKAP expression

Cited by 211 publications

References 21 publications

Vascular research using human pluripotent stem cells and humoral factors [Review]

Vascular research using human pluripotent stem cells and humoral factors [Review]

How iPS cells changed the world

Induced Pluripotent Stem Cell Models to Enable In Vitro Models for Screening in the Central Nervous System

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