Neural Differentiation of Human Pluripotent Stem Cells for Nontherapeutic Applications: Toxicology, Pharmacology, and<i>In Vitro</i>Disease Modeling

Yap, May Shin; Nathan, Kavitha R.; Yeo, Yin; Lim, Lee Wei; Poh, Chit Laa; Richards, Mark; Lim, Wei Ling; Othman, Iekhsan; Heng, Boon Chin

doi:10.1155/2015/105172

Cited by 28 publications

(29 citation statements)

References 112 publications

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“…Publications with human NPCs started to demonstrate their use in assessing toxicological profile of drugs [25,27]. Using hESC-derived NPCs, a research group described a platform for detection of toxicity to neuronal induction in embryonic development [28].…”

Section: The Current State-of-the-art Of Using Hpsc For Cns Safety Scmentioning

confidence: 99%

Using Human Pluripotent Stem Cell-Derived Neural Cultures to Assess Safety of New Drugs and Chemicals

Carromeu¹

2018

Neurotoxins

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The central nervous system (CNS) is a central pillar in safety pharmacology studies of new drugs. Characterization of serious adverse drug reactions to a new chemical entity involves extensive investigation using in vitro and in vivo models. However, primary culture of human neurons in vitro can be challenging, giving limited sample availability. Additionally, the inter-species differences between humans and current animal models impose a considerable obstacle to successfully predict the outcome of new drugs. New technologies also need to help address the 3Rs principles in animal research. Human pluripotent stem cells (hPSC) have the potential to change the current paradigm in pharmacological research. By using hPSCs and state-of-the-art differentiation protocols, researchers now have available an unlimited source of neural cells, able to mimic early and late stage of human CNS development. Moreover, hPSC-derived cells can be used at early stages of drug development, improving clinical predictability and reducing overall drug development costs. This chapter covers the advancements that resulted in hPSCderived models intended to enable neurotoxicity assessment and drug screening. Finally, this chapter will also reveal the bottlenecks and the challenges to overcome of using hPSC as a predictive tool in research.

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Section: The Current State-of-the-art Of Using Hpsc For Cns Safety Scmentioning

confidence: 99%

Using Human Pluripotent Stem Cell-Derived Neural Cultures to Assess Safety of New Drugs and Chemicals

Carromeu¹

2018

Neurotoxins

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“…The DPSCs promoted the regeneration of transacted axons by directly inhibiting multiple axon growth inhibitors and by prevention of apoptosis of neurons, astrocytes and oligodendrocytes. The DPSCs were then differentiated into mature oligodendrocytes to replace the cells that were lost (16,37,38,39,40).…”

Section: Neural Differentiationmentioning

confidence: 99%

“…DPSCs has also shown to be differentiated into cells with morphological, phenotype and functional characteristics similar to hepatocytes. It has been further suggested that the stem cells derived have the capacity to differentiate into hepatic family (37,38).…”

Section: Differentiation To Hepatocytementioning

confidence: 99%

Human Dental Pulp Stem Cells – A Prospective Regenerative Therapy

Tiwari¹

2018

IJTSRD

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Stem cells are the pluripotent cells that possess the potential to differentiate into a variety of cells of the human body. The knowledge of stem cell is enhancing not only in the medical field but equally in the dental field too. The stem cells of the dental origin provide remedies to many cell-based therapies in the regenerative medicine. Dental pulp stem cells (DPSCs) possess the mesenchymal stem cells phenotype and therefore get differentiated into neuron, chondrocytes, cardiomyocytes. The demand of cry preserving human exfoliated deciduous teeth (SHED) cells or the DPSCs are gaining popularity, in a similar fashion of the umbilical cord blood storage. The dental pulp stem cells are the adult multipotent cells that thrive in the cell abundant zone of the dental pulp. Accordingly, this multipotent characteristic makes the DPSCs an apt model to be incorporated in both dental and medical applications respectively. Therefore, this review which has been executed by both the electronic and hand-searching tools provides an outline of the applications of the dental pulp stem cells in the treatment of various medical disorders, nevertheless other aspects like the long-term clinical trials and studies needs more investigation to ascertain their efficacy.

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“…Further, the in vitro neural differentiation of PSCs recapitulates in vivo neural development (Abranches et al, 2009;Mertens et al, 2016), thereby making these cells a suitable model for neurodevelopmental studies. PSC-derived neural cells have been employed for toxicological studies, disease modeling, and drug screening (Avior et al, 2016;Marchetto et al, 2011;Yap et al, 2015). Most importantly, PSCs serve as an excellent source of cells for potential cell replacement for the treatment of various neurodegenerative diseases and disorders http://dx.doi.org/10.1016/j.ijdevneu.2017.06.009 Received 26 May 2017; Received in revised form 13 June 2017; Accepted 29 June 2017 (Jongkamonwiwat and Noisa, 2013).…”

Section: Introductionmentioning

confidence: 99%

Efficient neural differentiation of mouse pluripotent stem cells in a serum‐free medium and development of a novel strategy for enrichment of neural cells

Verma

Rashid

Sikdar

et al. 2017

Intl J of Devlp Neuroscience

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Pluripotent stem cells (PSCs) offer an excellent model to study neural development and function. Although various protocols have been developed to direct the differentiation of PSCs into desired neural cell types, many of them suffer from limitations including low efficiency, long duration of culture, and the use of expensive, labile, and undefined growth supplements. In this study, we achieved efficient differentiation of mouse PSCs to neural lineage, in the absence of exogenous molecules, by employing a serum-free culture medium containing knockout serum replacement (KSR). Embryoid bodies (EBs) cultured in this medium predominantly produced neural cells which included neural progenitors (15-18%), immature neurons (8-24%), mature neurons (10-26%), astrocytes (27-61%), and oligodendrocytes (∼1%). Different neuronal subtypes including glutamatergic, GABAergic, cholinergic, serotonergic, and dopaminergic neurons were generated. Importantly, neurons generated in the KSR medium were electrically active. Further, the EB scooping strategy, involving the removal of the EB core region from the peripheral EB outgrowth, resulted in the enrichment of PSC-derived neural cells. Taken together, this study provides the evidence that the KSR medium is ideal for the rapid and efficient generation of neural cells, including functional neurons, from PSCs without the requirement of any other additional molecule.

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Neural Differentiation of Human Pluripotent Stem Cells for Nontherapeutic Applications: Toxicology, Pharmacology, andIn VitroDisease Modeling

Cited by 28 publications

References 112 publications

Using Human Pluripotent Stem Cell-Derived Neural Cultures to Assess Safety of New Drugs and Chemicals

Using Human Pluripotent Stem Cell-Derived Neural Cultures to Assess Safety of New Drugs and Chemicals

Human Dental Pulp Stem Cells – A Prospective Regenerative Therapy

Efficient neural differentiation of mouse pluripotent stem cells in a serum‐free medium and development of a novel strategy for enrichment of neural cells

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