Induced pluripotent stem cells for modeling of pediatric neurological disorders

Jang, Jiho; Quan, Zhejiu; Yum, Yunjin J.; Song, Hae Jun; Paek, Seonyeol; Kang, Hoon Chul

doi:10.1002/biot.201400010

Cited by 13 publications

(7 citation statements)

References 95 publications

(89 reference statements)

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“…Stem cell derived 3D neuronal cultures have garnered interest because they have demonstrated utility in modeling neurological and neurodegenerative disorders (Choi et al, 2014; Jang et al, 2014). For example, by culturing human neural progenitor cells overexpressing genes associated with familial Alzheimer’s disease within 3D Matrigel, Choi et al were able to create an in vitro model that recapitulates the hallmark pathology of Alzheimer’s disease (Choi et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

High‐throughput identification of factors promoting neuronal differentiation of human neural progenitor cells in microscale 3D cell culture

Nierode

Gopal

Kwon

et al. 2018

Biotech & Bioengineering

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Identification of conditions for guided and specific differentiation of human stem cell and progenitor cells is important for continued development and engineering of in vitro cell culture systems for use in regenerative medicine, drug discovery, and human toxicology. Three-dimensional (3D) and organotypic cell culture models have been used increasingly for in vitro cell culture because they may better model endogenous tissue environments. However, detailed studies of stem cell differentiation within 3D cultures remain limited, particularly with respect to high-throughput screening. Herein, we demonstrate the use of a microarray chip-based platform to screen, in high-throughput, individual and paired effects of 12 soluble factors on the neuronal differentiation of a human neural progenitor cell line (ReNcell VM) encapsulated in microscale 3D Matrigel cultures. Dose-response analysis of selected combinations from the initial combinatorial screen revealed that the combined treatment of all-trans retinoic acid (RA) with the glycogen synthase kinase 3 inhibitor CHIR-99021 (CHIR) enhances neurogenesis while simultaneously decreases astrocyte differentiation, whereas the combined treatment of brain-derived neurotrophic factor and the small azide neuropathiazol enhances the differentiation into neurons and astrocytes. Subtype specification analysis of RA- and CHIR-differentiated cultures revealed that enhanced neurogenesis was not biased toward a specific neuronal subtype. Together, these results demonstrate a high-throughput screening platform for rapid evaluation of differentiation conditions in a 3D environment, which will aid the development and application of 3D stem cell culture models.

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Section: Introductionmentioning

confidence: 99%

High‐throughput identification of factors promoting neuronal differentiation of human neural progenitor cells in microscale 3D cell culture

Nierode

Gopal

Kwon

et al. 2018

Biotech & Bioengineering

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“…Currently, active research in differentiating iPSC towards definitive hematopoietic stem cells with long term engraftment potential is underway. In addition to their therapeutic potential, iPSCs can also be used as in-vitro disease models 67 . Off-target nuclease binding activity 68 , efficient means of delivering the genome editing tools to target stem cell populations without loss of 'stemness' , genomic variation occurring with somatic reprogramming, efficient gene targeting by homology directed repair 69 , and developing functional HSCs from these genetically modified iPSC 70,71 are some of the challenges in the field.…”

Section: Recent Advances In Genetic Manipulation Technologymentioning

confidence: 99%

Gene therapy for hemoglobin disorders - a mini-review

Rai¹

2016

J Rare Dis Res Treat

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Gene therapy by either gene insertion or editing is an exciting curative therapeutic option for monogenic hemoglobin disorders like sickle cell disease and β-thalassemia. The safety and efficacy of gene transfer techniques has markedly improved with the use of lentivirus vectors. The clinical translation of this technology has met with good success, although key limitations include number of engraftable transduced hematopoietic stem cells and adequate transgene expression that results in complete correction of β0 thalassemia major. This highlights the need to identify and address factors that might be contributing to the in-vivo survival of the transduced hematopoietic stem cells or find means to improve expression from current vectors. In this review, we briefly discuss the gene therapy strategies specific to hemoglobinopathies, the success of the preclinical models and the current status of gene therapy clinical trials.

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“…To date, patient-derived iPSC models for over 20 different neurodevelopmental or neurodegenerative disorders have been reported 6 , and this number is rapidly increasing. Those models relevant to epilepsy will be described below, but others include adrenoleukodystrophy, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), ataxia telangiectasia, Down syndrome, Friedreich’s ataxia, Huntington’s disease, Machado-Joseph disease, Niemann-Pick type C disease, Parkinson’s disease, primary microcephaly, schizophrenia, spinal muscular atrophy and others (see 6,28,29 and references therein).…”

Section: Ipsc Studies Of Cns Disordersmentioning

confidence: 99%

Reprogramming patient-derived cells to study the epilepsies

Parent

Anderson

2015

Nat Neurosci

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The epilepsies and related disorders of brain circuitry present significant challenges for using human cells to study disease mechanisms and develop new therapies. Some of these obstacles are being overcome with the use of induced pluripotent stem cell techniques to obtain patient-derived neural cells for in vitro studies and as a source of cell based treatments. The field is evolving rapidly with the addition of genome editing approaches and expanding protocols for generating different neural cell types and three-dimensional tissues, but the application to neurological disorders and particularly to the epilepsies is in its infancy. We discuss the progress made to date, the unique advantages and limitations of using patient-derived cells to study or treat epilepsy, and critical future directions for the field.

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Induced pluripotent stem cells for modeling of pediatric neurological disorders

Cited by 13 publications

References 95 publications

High‐throughput identification of factors promoting neuronal differentiation of human neural progenitor cells in microscale 3D cell culture

High‐throughput identification of factors promoting neuronal differentiation of human neural progenitor cells in microscale 3D cell culture

Gene therapy for hemoglobin disorders - a mini-review

Reprogramming patient-derived cells to study the epilepsies

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