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Cells
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The Current Applications and Potential of Human Pluripotent Stem Cells
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The Current Applications and Potential of Human Pluripotent Stem Cells

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 5911

Special Issue Editor

Dr. Leila Maouche-Chretien

E-Mail Website
Guest Editor
Laboratory of Molecular Mechanisms of Hematologic Disorders and Therapeutic Implications, INSERM UMR 1163, Imagine Institute, Paris-Centre University, F-75015 Paris, France
Interests: hematology; oncology; stem cells

Special Issue Information

Dear Colleagues,

We are excited to announce a Special Issue in our journal Cells on the current applications and potential of human pluripotent stem cells.

We invite researchers to submit original articles, reviews, and commentaries that showcase their expertise and contribute to advancing the field. Topics of interest include (but are not limited to) medical applications of pluripotent stem cells in regenerative medicine, research on genetic diseases, toxicology and pharmacology applications, and advances in culturing and differentiating human pluripotent stem cells. We welcome submissions that demonstrate the potential of organoids and biomaterials for various applications.

We hope to receive high-quality submissions that inspire new directions in research and demonstrate the potential of pluripotent stem cells, organoids, and biomaterials for various applications. For any inquiries related to this Special Issue, please contact the Editorial Office.

Dr. Leila Maouche-Chretien
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • human pluripotent stem cells
  • disease modeling
  • tissue engineering
  • organoids
  • regenerative medicine
  • epigenetic

Published Papers (5 papers)

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Research

Jump to: Review

16 pages, 3616 KiB  
Article
Human-Induced Pluripotent Stem Cell (iPSC)-Derived GABAergic Neuron Differentiation in Bipolar Disorder
by Daniel J. Schill, Durga Attili, Cynthia J. DeLong, Melvin G. McInnis, Craig N. Johnson, Geoffrey G. Murphy and K. Sue O’Shea
Cells 2024, 13(14), 1194; https://doi.org/10.3390/cells13141194 - 15 Jul 2024
Viewed by 692
Abstract
Bipolar disorder (BP) is a recurring psychiatric condition characterized by alternating episodes of low energy (depressions) followed by manias (high energy). Cortical network activity produced by GABAergic interneurons may be critical in maintaining the balance in excitatory/inhibitory activity in the brain during development. [...] Read more.
Bipolar disorder (BP) is a recurring psychiatric condition characterized by alternating episodes of low energy (depressions) followed by manias (high energy). Cortical network activity produced by GABAergic interneurons may be critical in maintaining the balance in excitatory/inhibitory activity in the brain during development. Initially, GABAergic signaling is excitatory; with maturation, these cells undergo a functional switch that converts GABAA channels from depolarizing (excitatory) to hyperpolarizing (inhibitory), which is controlled by the intracellular concentration of two chloride transporters. The earliest, NKCC1, promotes chloride entry into the cell and depolarization, while the second (KCC2) stimulates movement of chloride from the neuron, hyperpolarizing it. Perturbations in the timing or expression of NKCC1/KCC2 may affect essential morphogenetic events including cell proliferation, migration, synaptogenesis and plasticity, and thereby the structure and function of the cortex. We derived induced pluripotent stem cells (iPSC) from BP patients and undiagnosed control (C) individuals, then modified a differentiation protocol to form GABAergic interneurons, harvesting cells at sequential stages of differentiation. qRT-PCR and RNA sequencing indicated that after six weeks of differentiation, controls transiently expressed high levels of NKCC1. Using multi-electrode array (MEA) analysis, we observed that BP neurons exhibit increased firing, network bursting and decreased synchrony compared to C. Understanding GABA signaling in differentiation may identify novel approaches and new targets for treatment of neuropsychiatric disorders such as BP. Full article
(This article belongs to the Special Issue The Current Applications and Potential of Human Pluripotent Stem Cells)
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19 pages, 4275 KiB  
Article
Reduced Retinal Pigment Epithelial Autophagy Due to Loss of Rab12 Prenylation in a Human iPSC-RPE Model of Choroideremia
by Maide Ö. Raeker, Nirosha D. Perera, Athanasios J. Karoukis, Lisheng Chen, Kecia L. Feathers, Robin R. Ali, Debra A. Thompson and Abigail T. Fahim
Cells 2024, 13(12), 1068; https://doi.org/10.3390/cells13121068 - 19 Jun 2024
Viewed by 884
Abstract
Choroideremia is an X-linked chorioretinal dystrophy caused by mutations in CHM, encoding Rab escort protein 1 (REP-1), leading to under-prenylation of Rab GTPases (Rabs). Despite ubiquitous expression of CHM, the phenotype is limited to degeneration of the retina, retinal pigment epithelium [...] Read more.
Choroideremia is an X-linked chorioretinal dystrophy caused by mutations in CHM, encoding Rab escort protein 1 (REP-1), leading to under-prenylation of Rab GTPases (Rabs). Despite ubiquitous expression of CHM, the phenotype is limited to degeneration of the retina, retinal pigment epithelium (RPE), and choroid, with evidence for primary pathology in RPE cells. However, the spectrum of under-prenylated Rabs in RPE cells and how they contribute to RPE dysfunction remain unknown. A CRISPR/Cas-9-edited CHM−/− iPSC-RPE model was generated with isogenic control cells. Unprenylated Rabs were biotinylated in vitro and identified by tandem mass tag (TMT) spectrometry. Rab12 was one of the least prenylated and has an established role in suppressing mTORC1 signaling and promoting autophagy. CHM−/− iPSC-RPE cells demonstrated increased mTORC1 signaling and reduced autophagic flux, consistent with Rab12 dysfunction. Autophagic flux was rescued in CHM−/− cells by transduction with gene replacement (ShH10-CMV-CHM) and was reduced in control cells by siRNA knockdown of Rab12. This study supports Rab12 under-prenylation as an important cause of RPE cell dysfunction in choroideremia and highlights increased mTORC1 and reduced autophagy as potential disease pathways for further investigation. Full article
(This article belongs to the Special Issue The Current Applications and Potential of Human Pluripotent Stem Cells)
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16 pages, 13881 KiB  
Article
Single-Cell Transcriptomics and In Vitro Lineage Tracing Reveals Differential Susceptibility of Human iPSC-Derived Midbrain Dopaminergic Neurons in a Cellular Model of Parkinson’s Disease
by Lucia F. Cardo, Jimena Monzón-Sandoval, Zongze Li, Caleb Webber and Meng Li
Cells 2023, 12(24), 2860; https://doi.org/10.3390/cells12242860 - 18 Dec 2023
Cited by 2 | Viewed by 2107
Abstract
Advances in stem cell technologies open up new avenues for modelling development and diseases. The success of these pursuits, however, relies on the use of cells most relevant to those targeted by the disease of interest, for example, midbrain dopaminergic neurons for Parkinson’s [...] Read more.
Advances in stem cell technologies open up new avenues for modelling development and diseases. The success of these pursuits, however, relies on the use of cells most relevant to those targeted by the disease of interest, for example, midbrain dopaminergic neurons for Parkinson’s disease. In the present study, we report the generation of a human induced pluripotent stem cell (iPSC) line capable of purifying and tracing nascent midbrain dopaminergic progenitors and their differentiated progeny via the expression of a Blue Fluorescent Protein (BFP). This was achieved by CRISPR/Cas9-assisted knock-in of BFP and Cre into the safe harbour locus AAVS1 and an early midbrain dopaminergic lineage marker gene LMX1A, respectively. Immunocytochemical analysis and single-cell RNA sequencing of iPSC-derived neural cultures confirm developmental recapitulation of the human fetal midbrain and high-quality midbrain cells. By modelling Parkinson’s disease-related drug toxicity using 1-Methyl-4-phenylpyridinium (MPP+), we showed a preferential reduction of BFP+ cells, a finding demonstrated independently by cell death assays and single-cell transcriptomic analysis of MPP+ treated neural cultures. Together, these results highlight the importance of disease-relevant cell types in stem cell modelling. Full article
(This article belongs to the Special Issue The Current Applications and Potential of Human Pluripotent Stem Cells)
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Review

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15 pages, 689 KiB  
Review
Advancements in Research on Genetic Kidney Diseases Using Human-Induced Pluripotent Stem Cell-Derived Kidney Organoids
by Do Hyun Na, Sheng Cui, Xianying Fang, Hanbi Lee, Sang Hun Eum, Yoo Jin Shin, Sun Woo Lim, Chul Woo Yang and Byung Ha Chung
Cells 2024, 13(14), 1190; https://doi.org/10.3390/cells13141190 - 13 Jul 2024
Viewed by 466
Abstract
Genetic or hereditary kidney disease stands as a pivotal cause of chronic kidney disease (CKD). The proliferation and widespread utilization of DNA testing in clinical settings have notably eased the diagnosis of genetic kidney diseases, which were once elusive but are now increasingly [...] Read more.
Genetic or hereditary kidney disease stands as a pivotal cause of chronic kidney disease (CKD). The proliferation and widespread utilization of DNA testing in clinical settings have notably eased the diagnosis of genetic kidney diseases, which were once elusive but are now increasingly identified in cases previously deemed CKD of unknown etiology. However, despite these diagnostic strides, research into disease pathogenesis and novel drug development faces significant hurdles, chiefly due to the dearth of appropriate animal models and the challenges posed by limited patient cohorts in clinical studies. Conversely, the advent and utilization of human-induced pluripotent stem cells (hiPSCs) offer a promising avenue for genetic kidney disease research. Particularly, the development of hiPSC-derived kidney organoid systems presents a novel platform for investigating various forms of genetic kidney diseases. Moreover, the integration of the CRISPR/Cas9 technique into this system holds immense potential for efficient research on genetic kidney diseases. This review aims to explore the applications of in vitro kidney organoids generated from hiPSCs in the study of diverse genetic kidney diseases. Additionally, it will delve into the limitations of this research platform and outline future perspectives for advancing research in this crucial area. Full article
(This article belongs to the Special Issue The Current Applications and Potential of Human Pluripotent Stem Cells)
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23 pages, 1553 KiB  
Review
Cell-Based Therapy for Fibrosing Interstitial Lung Diseases, Current Status, and Potential Applications of iPSC-Derived Cells
by Yusuke Nakamura, Seiji Niho and Yasuo Shimizu
Cells 2024, 13(11), 893; https://doi.org/10.3390/cells13110893 - 22 May 2024
Viewed by 938
Abstract
Fibrosing interstitial lung diseases (FILDs), e.g., due to idiopathic pulmonary fibrosis (IPF), are chronic progressive diseases with a poor prognosis. The management of these diseases is challenging and focuses mainly on the suppression of progression with anti-fibrotic drugs. Therefore, novel FILD treatments are [...] Read more.
Fibrosing interstitial lung diseases (FILDs), e.g., due to idiopathic pulmonary fibrosis (IPF), are chronic progressive diseases with a poor prognosis. The management of these diseases is challenging and focuses mainly on the suppression of progression with anti-fibrotic drugs. Therefore, novel FILD treatments are needed. In recent years, cell-based therapy with various stem cells has been investigated for FILD, and the use of mesenchymal stem cells (MSCs) has been widely reported and clinical studies are also ongoing. Induced pluripotent stem cells (iPSCs) have also been reported to have an anti-fibrotic effect in FILD; however, these have not been as well studied as MSCs in terms of the mechanisms and side effects. While MSCs show a potent anti-fibrotic effect, the possibility of quality differences between donors and a stable supply in the case of donor shortage or reduced proliferative capacity after cell passaging needs to be considered. The application of iPSC-derived cells has the potential to overcome these problems and may lead to consistent quality of the cell product and stable product supply. This review provides an overview of iPSCs and FILD, followed by the current status of cell-based therapy for FILD, and then discusses the possibilities and perspectives of FILD therapy with iPSC-derived cells. Full article
(This article belongs to the Special Issue The Current Applications and Potential of Human Pluripotent Stem Cells)
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