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Human Pluripotent Stem Cell-Based Disease Modeling

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A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Medical Biology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 11854

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Special Issue Editors

Dr. Yohan Oh

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Guest Editor

Department of Biomedical Science, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, Republic of Korea
Interests: stem cell biology; pluripotent stem cell; disease modeling; neuroscience; signal transduction; developmental biology; sympathetic neuron; optogenetics; molecular biology; cell biology

Dr. Yong Jun Kim

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Guest Editor

Department of Pathology, College of Medicine, Kyung Hee University, Seoul, Korea
Interests: molecular pathology in human neurological and/or developmental diseases; fate control of human embryonic stem cells

Dr. Dae-Sung Kim

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Guest Editor

Department of Biotechnology, College of Life Science & Biotechnology, Korea University, Seoul, Korea
Interests: In vitro disease model and drug screening system using pluripotent stem cells (PSCs); The central nervous system (CNS) disease; The mechanisms of mammalian neural development

Special Issue Information

Dear Colleagues,

Human pluripotent stem cells (hPSCs), including embryonic stem or induced pluripotent stem cells (hESCs/hiPSCs), differentiated into specific types of cells have been accepted as a promising model for studying human disease and as potential cell sources for transplantation. Particularly, disease-specific hiPSCs provide us with an exceptional opportunity to recapitulate human disease phenotypes in vitro, thereby enabling disease investigation and drug development; although, there are several challenges which need to be addressed.

In this Special Issue, we respectfully invite original research (articles, short communications, and reviews) addressing the following topics:

Development of hPSC-based disease models;
Improvement of hPSC-based disease models;
Application of hPSC-based disease models;
Generation of hPSC-derived human cells or organoids;
Development of hPSC-based cell therapies;
Optimization of hPSC-based cell therapies.

We hope that this Special Issue will highlight the power of stem-cell-based approaches for asking fundamental disease questions with regard to human cells.

Dr. Yohan Oh
Dr. Yong Jun Kim
Dr. Dae-Sung Kim
Guest Editors

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Keywords

pluripotent stem cell
hPSC
hESC
hiPSC
disease modeling
cell therapy
differentiation
organoid
transplantation

Published Papers (3 papers)

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Research

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13 pages, 3547 KiB

Open AccessArticle

Elimination of Reprogramming Transgenes Facilitates the Differentiation of Induced Pluripotent Stem Cells into Hepatocyte-like Cells and Hepatic Organoids

by Jaemin Jeong, Tae Hun Kim, Myounghoi Kim, Yun Kyung Jung, Kyeong Sik Kim, Sehwan Shim, Hyosun Jang, Won Il Jang, Seung Bum Lee and Dongho Choi

Biology 2022, 11(4), 493; https://0-doi-org.brum.beds.ac.uk/10.3390/biology11040493 - 23 Mar 2022

Cited by 3 | Viewed by 2570

Abstract

Hepatocytes and hepatic organoids (HOs) derived from human induced pluripotent stem cells (hiPSCs) are promising cell-based therapies for liver diseases. The removal of reprogramming transgenes can affect hiPSC differentiation potential into the three germ layers but not into hepatocytes and hepatic organoids in the late developmental stage. Herein, we generated hiPSCs from normal human fibroblasts using an excisable polycistronic lentiviral vector based on the Cre recombinase-mediated removal of the loxP-flanked reprogramming cassette. Comparing the properties of transgene-carrying and transgene-free hiPSCs with the same genetic background, the pluripotent states of all hiPSCs were quite similar, as indicated by the expression of pluripotent markers, embryonic body formation, and tri-lineage differentiation in vitro. However, after in vitro differentiation into hepatocytes, transgene-free hiPSCs were superior to the transgene-residual hiPSCs. Interestingly, the generation and hepatic differentiation of human hepatic organoids (hHOs) were significantly enhanced by transgene elimination from hiPSCs, as observed by the upregulated fetal liver (CK19, SOX9, and ITGA6) and functional hepatocyte (albumin, ASGR1, HNF4α, CYP1A2, CYP3A4, and AAT) markers upon culture in differentiation media. Thus, the elimination of reprogramming transgenes facilitates hiPSC differentiation into hepatocyte-like cells and hepatic organoids with properties of liver progenitor cells. Our findings thus provide significant insights into the characteristics of iPSC-derived hepatic organoids. Full article

(This article belongs to the Special Issue Human Pluripotent Stem Cell-Based Disease Modeling)

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16 pages, 5056 KiB

Open AccessArticle

A Novel Vitronectin Peptide Facilitates Differentiation of Oligodendrocytes from Human Pluripotent Stem Cells (Synthetic ECM for Oligodendrocyte Differentiation)

by Won Ung Park, Gyu-Bum Yeon, Myeong-Sang Yu, Hui-Gwan Goo, Su-Hee Hwang, Dokyun Na and Dae-Sung Kim

Biology 2021, 10(12), 1254; https://0-doi-org.brum.beds.ac.uk/10.3390/biology10121254 - 01 Dec 2021

Cited by 5 | Viewed by 2148

Abstract

Differentiation of oligodendrocytes (ODs) presents a challenge in regenerative medicine due to their role in various neurological diseases associated with dysmyelination and demyelination. Here, we designed a peptide derived from vitronectin (VN) using in silico docking simulation and examined its use as a synthetic substrate to support the differentiation of ODs derived from human pluripotent stem cells. The designed peptide, named VNP2, promoted OD differentiation induced by the overexpression of SOX10 in OD precursor cells compared with Matrigel and full-length VN. ODs differentiated on VNP2 exhibited greater contact with axon-mimicking nanofibers than those differentiated on Matrigel. Transcriptomic analysis revealed that the genes associated with morphogenesis, cytoskeleton remodeling, and OD differentiation were upregulated in cells grown on VNP2 compared with cells grown on Matrigel. This new synthetic VN-derived peptide can be used to develop a culture environment for efficient OD differentiation. Full article

(This article belongs to the Special Issue Human Pluripotent Stem Cell-Based Disease Modeling)

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Review

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28 pages, 1002 KiB

Open AccessReview

Multielectrode Arrays for Functional Phenotyping of Neurons from Induced Pluripotent Stem Cell Models of Neurodevelopmental Disorders

by Fraser P. McCready, Sara Gordillo-Sampedro, Kartik Pradeepan, Julio Martinez-Trujillo and James Ellis

Biology 2022, 11(2), 316; https://0-doi-org.brum.beds.ac.uk/10.3390/biology11020316 - 16 Feb 2022

Cited by 15 | Viewed by 6293

Abstract

In vitro multielectrode array (MEA) systems are increasingly used as higher-throughput platforms for functional phenotyping studies of neurons in induced pluripotent stem cell (iPSC) disease models. While MEA systems generate large amounts of spatiotemporal activity data from networks of iPSC-derived neurons, the downstream analysis and interpretation of such high-dimensional data often pose a significant challenge to researchers. In this review, we examine how MEA technology is currently deployed in iPSC modeling studies of neurodevelopmental disorders. We first highlight the strengths of in vitro MEA technology by reviewing the history of its development and the original scientific questions MEAs were intended to answer. Methods of generating patient iPSC-derived neurons and astrocytes for MEA co-cultures are summarized. We then discuss challenges associated with MEA data analysis in a disease modeling context, and present novel computational methods used to better interpret network phenotyping data. We end by suggesting best practices for presenting MEA data in research publications, and propose that the creation of a public MEA data repository to enable collaborative data sharing would be of great benefit to the iPSC disease modeling community. Full article

(This article belongs to the Special Issue Human Pluripotent Stem Cell-Based Disease Modeling)

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