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iPS Cells for Disease Modeling
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iPS Cells for Disease Modeling

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

Deadline for manuscript submissions: closed (30 September 2019) | Viewed by 88692

Special Issue Editors

Dr. Lezanne Ooi

E-Mail Website
Guest Editor
Illawarra Health and Medical Research Institute, School of Biological Sciences, University of Wollongong, Wollongong, Australia
Interests: induced pluripotent stem cells; neurodegeneration; neurodevelopment; neuroprotection; Alzheimer’s disease; motor neuron disease; dementia
Special Issues, Collections and Topics in MDPI journals
Dr. Mirella Dottori

E-Mail Website
Guest Editor
Illawarra Health and Medical Research Institute, School of Medicine, University of Wollongong, Wollongong, Australia
Interests: human pluripotent stem cells; neurodevelopment; peripheral sensory neurons; neurodegeneration; Friedreich’s ataxia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleauges,

There is a growing appreciation that the use of human cells in vitro is important for preclinical drug testing and identifying disease mechanisms that can lead to the development of novel therapeutic strategies. The use of induced pluripotent stem cells (iPSCs) for disease modelling and drug discovery has thus exploded over the last decade and almost every disease can be modelled in vitro. Central to the utility of iPSCs is the development of protocols that yield functional disease-relevant cell types that recapitulate disease phenotypes. The aim of this Special Issue is to provide protocols and assays that are used in iPSC disease modelling and to highlight the strengths and weaknesses of the approaches currently available. The articles will be a valuable resource for the disease modelling scientific community.

Dr. Lezanne Ooi
Prof. Mirella Dottori
Guest Editors

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

  • induced pluripotent stem cells
  • pluripotent stem cells
  • disease modelling
  • drug discovery
  • differentiation
  • functional characterisation
  • cell phenotype

Related Special Issue

Published Papers (12 papers)

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Research

Jump to: Review

18 pages, 5062 KiB  
Article
Human iPSCs-Derived Endothelial Cells with Mutation in HNF1A as a Model of Maturity-Onset Diabetes of the Young
by Neli Kachamakova-Trojanowska, Jacek Stepniewski and Jozef Dulak
Cells 2019, 8(11), 1440; https://doi.org/10.3390/cells8111440 - 14 Nov 2019
Cited by 16 | Viewed by 4586
Abstract
Patients with HNF1A-maturity-onset diabetes of the young (MODY) often develop endothelial dysfunction and related microvascular complications, like retinopathy. As the clinical phenotype of HNF1A-MODY diabetes varies considerably, we used human induced pluripotent stem cells (hiPSCs) from two healthy individuals (control) to [...] Read more.
Patients with HNF1A-maturity-onset diabetes of the young (MODY) often develop endothelial dysfunction and related microvascular complications, like retinopathy. As the clinical phenotype of HNF1A-MODY diabetes varies considerably, we used human induced pluripotent stem cells (hiPSCs) from two healthy individuals (control) to generate isogenic lines with mutation in HNF1A gene. Subsequently, control hiPSCs and their respective HNF1A clones were differentiated toward endothelial cells (hiPSC-ECs) and different markers/functions were compared. Human iPSC-ECs from all cell lines showed similar expression of CD31 and Tie-2. VE-cadherin expression was lower in HNF1A-mutated isogenic lines, but only in clones derived from one control hiPSCs. In the other isogenic set and cells derived from HNF1A-MODY patients, no difference in VE-cadherin expression was observed, suggesting the impact of the genetic background on this endothelial marker. All tested hiPSC-ECs showed an expected angiogenic response regardless of the mutation introduced. Isogenic hiPSC-ECs responded similarly to stimulation with pro-inflammatory cytokine TNF-α with the increase in ICAM-1 and permeability, however, HNF1A mutated hiPSC-ECs showed higher permeability in comparison to the control cells. Summarizing, both mono- and biallelic mutations of HNF1A in hiPSC-ECs lead to increased permeability in response to TNF-α in normal glycemic conditions, which may have relevance to HNF1A-MODY microvascular complications. Full article
(This article belongs to the Special Issue iPS Cells for Disease Modeling)
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15 pages, 3727 KiB  
Article
Differentiation of Baboon (Papio anubis) Induced-Pluripotent Stem Cells into Enucleated Red Blood Cells
by Emmanuel N. Olivier, Kai Wang, Joshua Grossman, Nadim Mahmud and Eric E. Bouhassira
Cells 2019, 8(10), 1282; https://doi.org/10.3390/cells8101282 - 19 Oct 2019
Cited by 3 | Viewed by 4584
Abstract
As cell culture methods and stem cell biology have progressed, the in vitro production of cultured RBCs (cRBCs) has emerged as a viable option to produce cells for transfusion or to carry therapeutic cargoes. RBCs produced in culture can be quality-tested either by [...] Read more.
As cell culture methods and stem cell biology have progressed, the in vitro production of cultured RBCs (cRBCs) has emerged as a viable option to produce cells for transfusion or to carry therapeutic cargoes. RBCs produced in culture can be quality-tested either by xeno-transfusion of human cells into immuno-deficient animals, or by transfusion of autologous cells in immuno-competent models. Although murine xeno-transfusion methods have improved, they must be complemented by studies in immuno-competent models. Non-human primates (NHPs) are important pre-clinical, large animal models due to their high biological and developmental similarities with humans, including their comparable hematopoietic and immune systems. Among NHPs, baboons are particularly attractive to validate cRBCs because of the wealth of data available on the characteristics of RBCs in this species that have been generated by past blood transfusion studies. We report here that we have developed a method to produce enucleated cRBCs by differentiation of baboon induced pluripotent stem cells (iPSCs). This method will enable the use of baboons to evaluate therapeutic cRBCs and generate essential pre-clinical data in an immuno-competent, large animal model. Production of the enucleated baboon cRBCs was achieved by adapting the PSC-RED protocol that we previously developed for human cells. Baboon-PSC-RED is an efficient chemically-defined method to differentiate iPSCs into cRBCs that are about 40% to 50% enucleated. PSC-RED is relatively low cost because it requires no albumin and only small amounts of recombinant transferrin. Full article
(This article belongs to the Special Issue iPS Cells for Disease Modeling)
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18 pages, 4475 KiB  
Article
Ketamine Increases Proliferation of Human iPSC-Derived Neuronal Progenitor Cells via Insulin-Like Growth Factor 2 and Independent of the NMDA Receptor
by Alessandra Grossert, Narges Zare Mehrjardi, Sarah J. Bailey, Mark A. Lindsay, Jürgen Hescheler, Tomo Šarić and Nicole Teusch
Cells 2019, 8(10), 1139; https://doi.org/10.3390/cells8101139 - 24 Sep 2019
Cited by 10 | Viewed by 5958
Abstract
The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine offers promising perspectives for the treatment of major depressive disorder. Although ketamine demonstrates rapid and long-lasting effects, even in treatment-resistant patients, to date, the underlying mode of action remains elusive. Thus, the aim of our study was [...] Read more.
The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine offers promising perspectives for the treatment of major depressive disorder. Although ketamine demonstrates rapid and long-lasting effects, even in treatment-resistant patients, to date, the underlying mode of action remains elusive. Thus, the aim of our study was to investigate the molecular mechanism of ketamine at clinically relevant concentrations by establishing an in vitro model based on human induced pluripotent stem cells (iPSCs)-derived neural progenitor cells (NPCs). Notably, ketamine increased the proliferation of NPCs independent of the NMDA receptor, while transcriptome analysis revealed significant upregulation of insulin-like growth factor 2 (IGF2) and p11, a member of the S100 EF-hand protein family, which are both implicated in the pathophysiology of depression, 24 h after ketamine treatment. Ketamine (1 µM) was able to increase cyclic adenosine monophosphate (cAMP) signaling in NPCs within 15 min and cell proliferation, while ketamine-induced IGF2 expression was reduced after PKA inhibition with cAMPS-Rp. Furthermore, 24 h post-administration of ketamine (15 mg/kg) in vivo confirmed phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in the subgranular zone (SGZ) of the hippocampus in C57BL/6 mice. In conclusion, ketamine promotes the proliferation of NPCs presumably by involving cAMP-IGF2 signaling. Full article
(This article belongs to the Special Issue iPS Cells for Disease Modeling)
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21 pages, 2606 KiB  
Article
A Novel Chromosomal Translocation Identified due to Complex Genetic Instability in iPSC Generated for Choroideremia
by Nejla Erkilic, Vincent Gatinois, Simona Torriano, Pauline Bouret, Carla Sanjurjo-Soriano, Valerie De Luca, Krishna Damodar, Nicolas Cereso, Jacques Puechberty, Rocio Sanchez-Alcudia, Christian P. Hamel, Carmen Ayuso, Isabelle Meunier, Franck Pellestor and Vasiliki Kalatzis
Cells 2019, 8(9), 1068; https://doi.org/10.3390/cells8091068 - 11 Sep 2019
Cited by 4 | Viewed by 2966
Abstract
Induced pluripotent stem cells (iPSCs) have revolutionized the study of human diseases as they can renew indefinitely, undergo multi-lineage differentiation, and generate disease-specific models. However, the difficulty of working with iPSCs is that they are prone to genetic instability. Furthermore, genetically unstable iPSCs [...] Read more.
Induced pluripotent stem cells (iPSCs) have revolutionized the study of human diseases as they can renew indefinitely, undergo multi-lineage differentiation, and generate disease-specific models. However, the difficulty of working with iPSCs is that they are prone to genetic instability. Furthermore, genetically unstable iPSCs are often discarded, as they can have unforeseen consequences on pathophysiological or therapeutic read-outs. We generated iPSCs from two brothers of a previously unstudied family affected with the inherited retinal dystrophy choroideremia. We detected complex rearrangements involving chromosomes 12, 20 and/or 5 in the generated iPSCs. Suspecting an underlying chromosomal aberration, we performed karyotype analysis of the original fibroblasts, and of blood cells from additional family members. We identified a novel chromosomal translocation t(12;20)(q24.3;q11.2) segregating in this family. We determined that the translocation was balanced and did not impact subsequent retinal differentiation. We show for the first time that an undetected genetic instability in somatic cells can breed further instability upon reprogramming. Therefore, the detection of chromosomal aberrations in iPSCs should not be disregarded, as they may reveal rearrangements segregating in families. Furthermore, as such rearrangements are often associated with reproductive failure or birth defects, this in turn has important consequences for genetic counseling of family members. Full article
(This article belongs to the Special Issue iPS Cells for Disease Modeling)
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21 pages, 4124 KiB  
Article
Modeling of LMNA-Related Dilated Cardiomyopathy Using Human Induced Pluripotent Stem Cells
by Disheet Shah, Laura Virtanen, Chandra Prajapati, Mostafa Kiamehr, Josef Gullmets, Gun West, Joose Kreutzer, Mari Pekkanen-Mattila, Tiina Heliö, Pasi Kallio, Pekka Taimen and Katriina Aalto-Setälä
Cells 2019, 8(6), 594; https://doi.org/10.3390/cells8060594 - 15 Jun 2019
Cited by 40 | Viewed by 7498
Abstract
Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure and heart transplantation. A portion of familial DCM is due to mutations in the LMNA gene encoding the nuclear lamina proteins lamin A and C and without adequate treatment these patients [...] Read more.
Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure and heart transplantation. A portion of familial DCM is due to mutations in the LMNA gene encoding the nuclear lamina proteins lamin A and C and without adequate treatment these patients have a poor prognosis. To get better insights into pathobiology behind this disease, we focused on modeling LMNA-related DCM using human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM). Primary skin fibroblasts from DCM patients carrying the most prevalent Finnish founder mutation (p.S143P) in LMNA were reprogrammed into hiPSCs and further differentiated into cardiomyocytes (CMs). The cellular structure, functionality as well as gene and protein expression were assessed in detail. While mutant hiPSC-CMs presented virtually normal sarcomere structure under normoxia, dramatic sarcomere damage and an increased sensitivity to cellular stress was observed after hypoxia. A detailed electrophysiological evaluation revealed bradyarrhythmia and increased occurrence of arrhythmias in mutant hiPSC-CMs on β-adrenergic stimulation. Mutant hiPSC-CMs also showed increased sensitivity to hypoxia on microelectrode array and altered Ca2+ dynamics. Taken together, p.S143P hiPSC-CM model mimics hallmarks of LMNA-related DCM and provides a useful tool to study the underlying cellular mechanisms of accelerated cardiac degeneration in this disease. Full article
(This article belongs to the Special Issue iPS Cells for Disease Modeling)
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17 pages, 12392 KiB  
Article
The Ubiquitin Proteasome System Is a Key Regulator of Pluripotent Stem Cell Survival and Motor Neuron Differentiation
by Monique Bax, Jessie McKenna, Dzung Do-Ha, Claire H. Stevens, Sarah Higginbottom, Rachelle Balez, Mauricio e Castro Cabral-da-Silva, Natalie E. Farrawell, Martin Engel, Philip Poronnik, Justin J. Yerbury, Darren N. Saunders and Lezanne Ooi
Cells 2019, 8(6), 581; https://doi.org/10.3390/cells8060581 - 13 Jun 2019
Cited by 32 | Viewed by 10075
Abstract
The ubiquitin proteasome system (UPS) plays an important role in regulating numerous cellular processes, and a dysfunctional UPS is thought to contribute to motor neuron disease. Consequently, we sought to map the changing ubiquitome in human iPSCs during their pluripotent stage and following [...] Read more.
The ubiquitin proteasome system (UPS) plays an important role in regulating numerous cellular processes, and a dysfunctional UPS is thought to contribute to motor neuron disease. Consequently, we sought to map the changing ubiquitome in human iPSCs during their pluripotent stage and following differentiation to motor neurons. Ubiquitinomics analysis identified that spliceosomal and ribosomal proteins were more ubiquitylated in pluripotent stem cells, whilst proteins involved in fatty acid metabolism and the cytoskeleton were specifically ubiquitylated in the motor neurons. The UPS regulator, ubiquitin-like modifier activating enzyme 1 (UBA1), was increased 36-fold in the ubiquitome of motor neurons compared to pluripotent stem cells. Thus, we further investigated the functional consequences of inhibiting the UPS and UBA1 on motor neurons. The proteasome inhibitor MG132, or the UBA1-specific inhibitor PYR41, significantly decreased the viability of motor neurons. Consistent with a role of the UPS in maintaining the cytoskeleton and regulating motor neuron differentiation, UBA1 inhibition also reduced neurite length. Pluripotent stem cells were extremely sensitive to MG132, showing toxicity at nanomolar concentrations. The motor neurons were more resilient to MG132 than pluripotent stem cells but demonstrated higher sensitivity than fibroblasts. Together, this data highlights the important regulatory role of the UPS in pluripotent stem cell survival and motor neuron differentiation. Full article
(This article belongs to the Special Issue iPS Cells for Disease Modeling)
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18 pages, 4061 KiB  
Article
Oxidative Insults and Mitochondrial DNA Mutation Promote Enhanced Autophagy and Mitophagy Compromising Cell Viability in Pluripotent Cell Model of Mitochondrial Disease
by Dar-Shong Lin, Yu-Wen Huang, Che-Sheng Ho, Pi-Lien Hung, Mei-Hsin Hsu, Tuan-Jen Wang, Tsu-Yen Wu, Tsung-Han Lee, Zo-Darr Huang, Po-Chun Chang and Ming-Fu Chiang
Cells 2019, 8(1), 65; https://doi.org/10.3390/cells8010065 - 17 Jan 2019
Cited by 51 | Viewed by 9046
Abstract
Dysfunction of mitochondria causes defects in oxidative phosphorylation system (OXPHOS) and increased production of reactive oxygen species (ROS) triggering the activation of the cell death pathway that underlies the pathogenesis of aging and various diseases. The process of autophagy to degrade damaged cytoplasmic [...] Read more.
Dysfunction of mitochondria causes defects in oxidative phosphorylation system (OXPHOS) and increased production of reactive oxygen species (ROS) triggering the activation of the cell death pathway that underlies the pathogenesis of aging and various diseases. The process of autophagy to degrade damaged cytoplasmic components as well as dysfunctional mitochondria is essential for ensuring cell survival. We analyzed the role of autophagy inpatient-specific induced pluripotent stem (iPS) cells generated from fibroblasts of patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) with well-characterized mitochondrial DNA mutations and distinct OXPHOS defects. MELAS iPS cells recapitulated the pathogenesis of MELAS syndrome, and showed an increase of autophagy in comparison with its isogenic normal counterpart, whereas mitophagy is very scarce at the basal condition. Our results indicated that the existence of pathogenic mtDNA alone in mitochondrial disease was not sufficient to elicit the degradation of dysfunctional mitochondria. Nonetheless, oxidative insults induced bulk macroautophagy with the accumulation of autophagosomes and autolysosomes upon marked elevation of ROS, overload of intracellular calcium, and robust depolarization of mitochondrial membrane potential, while mitochondria respiratory function was impaired and widespread mitophagy compromised cell viability. Collectively, our studies provide insights into the dysfunction of autophagy and activation of mitophagy contributing to the pathological mechanism of mitochondrial disease. Full article
(This article belongs to the Special Issue iPS Cells for Disease Modeling)
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22 pages, 2566 KiB  
Article
Dystrophin Deficiency Leads to Genomic Instability in Human Pluripotent Stem Cells via NO Synthase-Induced Oxidative Stress
by Sarka Jelinkova, Petr Fojtik, Aneta Kohutova, Aleksandra Vilotic, Lenka Marková, Martin Pesl, Tereza Jurakova, Miriama Kruta, Jan Vrbsky, Renata Gaillyova, Iveta Valášková, Ivan Frák, Alain Lacampagne, Giancarlo Forte, Petr Dvorak, Albano C. Meli and Vladimir Rotrekl
Cells 2019, 8(1), 53; https://doi.org/10.3390/cells8010053 - 15 Jan 2019
Cited by 29 | Viewed by 6437
Abstract
Recent data on Duchenne muscular dystrophy (DMD) show myocyte progenitor’s involvement in the disease pathology often leading to the DMD patient’s death. The molecular mechanism underlying stem cell impairment in DMD has not been described. We created dystrophin-deficient human pluripotent stem cell (hPSC) [...] Read more.
Recent data on Duchenne muscular dystrophy (DMD) show myocyte progenitor’s involvement in the disease pathology often leading to the DMD patient’s death. The molecular mechanism underlying stem cell impairment in DMD has not been described. We created dystrophin-deficient human pluripotent stem cell (hPSC) lines by reprogramming cells from two DMD patients, and also by introducing dystrophin mutation into human embryonic stem cells via CRISPR/Cas9. While dystrophin is expressed in healthy hPSC, its deficiency in DMD hPSC lines induces the release of reactive oxygen species (ROS) through dysregulated activity of all three isoforms of nitric oxide synthase (further abrev. as, NOS). NOS-induced ROS release leads to DNA damage and genomic instability in DMD hPSC. We were able to reduce both the ROS release as well as DNA damage to the level of wild-type hPSC by inhibiting NOS activity. Full article
(This article belongs to the Special Issue iPS Cells for Disease Modeling)
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14 pages, 2817 KiB  
Article
Transfer of Synthetic Human Chromosome into Human Induced Pluripotent Stem Cells for Biomedical Applications
by Sergey A. Sinenko, Elena V. Skvortsova, Mikhail A. Liskovykh, Sergey V. Ponomartsev, Andrey A. Kuzmin, Aleksandr A. Khudiakov, Anna B. Malashicheva, Natalia Alenina, Vladimir Larionov, Natalay Kouprina and Alexey N. Tomilin
Cells 2018, 7(12), 261; https://doi.org/10.3390/cells7120261 - 8 Dec 2018
Cited by 19 | Viewed by 6100
Abstract
AlphoidtetO-type human artificial chromosome (HAC) has been recently synthetized as a novel class of gene delivery vectors for induced pluripotent stem cell (iPSC)-based tissue replacement therapeutic approach. This HAC vector was designed to deliver copies of genes into patients with genetic [...] Read more.
AlphoidtetO-type human artificial chromosome (HAC) has been recently synthetized as a novel class of gene delivery vectors for induced pluripotent stem cell (iPSC)-based tissue replacement therapeutic approach. This HAC vector was designed to deliver copies of genes into patients with genetic diseases caused by the loss of a particular gene function. The alphoidtetO-HAC vector has been successfully transferred into murine embryonic stem cells (ESCs) and maintained stably as an independent chromosome during the proliferation and differentiation of these cells. Human ESCs and iPSCs have significant differences in culturing conditions and pluripotency state in comparison with the murine naïve-type ESCs and iPSCs. To date, transferring alphoidtetO-HAC vector into human iPSCs (hiPSCs) remains a challenging task. In this study, we performed the microcell-mediated chromosome transfer (MMCT) of alphoidtetO-HAC expressing the green fluorescent protein into newly generated hiPSCs. We used a recently modified MMCT method that employs an envelope protein of amphotropic murine leukemia virus as a targeting cell fusion agent. Our data provide evidence that a totally artificial vector, alphoidtetO-HAC, can be transferred and maintained in human iPSCs as an independent autonomous chromosome without affecting pluripotent properties of the cells. These data also open new perspectives for implementing alphoidtetO-HAC as a gene therapy tool in future biomedical applications. Full article
(This article belongs to the Special Issue iPS Cells for Disease Modeling)
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Review

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21 pages, 1099 KiB  
Review
iPSCs-Based Neural 3D Systems: A Multidimensional Approach for Disease Modeling and Drug Discovery
by Gianluca Costamagna, Luca Andreoli, Stefania Corti and Irene Faravelli
Cells 2019, 8(11), 1438; https://doi.org/10.3390/cells8111438 - 14 Nov 2019
Cited by 24 | Viewed by 5793
Abstract
Induced pluripotent stem cells (iPSCs)-based two-dimensional (2D) protocols have offered invaluable insights into the pathophysiology of neurological diseases. However, these systems are unable to reproduce complex cytoarchitectural features, cell-cell and tissue-tissue interactions like their in vivo counterpart. Three-dimensional (3D)-based culture protocols, though in [...] Read more.
Induced pluripotent stem cells (iPSCs)-based two-dimensional (2D) protocols have offered invaluable insights into the pathophysiology of neurological diseases. However, these systems are unable to reproduce complex cytoarchitectural features, cell-cell and tissue-tissue interactions like their in vivo counterpart. Three-dimensional (3D)-based culture protocols, though in their infancy, have offered new insights into modeling human diseases. Human neural organoids try to recapitulate the cellular diversity of complex tissues and can be generated from iPSCs to model the pathophysiology of a wide spectrum of pathologies. The engraftment of iPSCs into mice models and the improvement of differentiation protocols towards 3D cultures has enabled the generation of more complex multicellular systems. Consequently, models of neuropsychiatric disorders, infectious diseases, brain cancer and cerebral hypoxic injury can now be investigated from new perspectives. In this review, we consider the advancements made in modeling neuropsychiatric and neurological diseases with iPSC-derived organoids and their potential use to develop new drugs. Full article
(This article belongs to the Special Issue iPS Cells for Disease Modeling)
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11 pages, 792 KiB  
Review
Use of Human Pluripotent Stem Cells to Define Initiating Molecular Mechanisms of Cataract for Anti-Cataract Drug Discovery
by Chitra Umala Dewi and Michael D. O’Connor
Cells 2019, 8(10), 1269; https://doi.org/10.3390/cells8101269 - 17 Oct 2019
Cited by 6 | Viewed by 3415
Abstract
Cataract is a leading cause of blindness worldwide. Currently, restoration of vision in cataract patients requires surgical removal of the cataract. Due to the large and increasing number of cataract patients, the annual cost of surgical cataract treatment amounts to billions of dollars. [...] Read more.
Cataract is a leading cause of blindness worldwide. Currently, restoration of vision in cataract patients requires surgical removal of the cataract. Due to the large and increasing number of cataract patients, the annual cost of surgical cataract treatment amounts to billions of dollars. Limited access to functional human lens tissue during the early stages of cataract formation has hampered efforts to develop effective anti-cataract drugs. The ability of human pluripotent stem (PS) cells to make large numbers of normal or diseased human cell types raises the possibility that human PS cells may provide a new avenue for defining the molecular mechanisms responsible for different types of human cataract. Towards this end, methods have been established to differentiate human PS cells into both lens cells and transparent, light-focusing human micro-lenses. Sensitive and quantitative assays to measure light transmittance and focusing ability of human PS cell-derived micro-lenses have also been developed. This review will, therefore, examine how human PS cell-derived lens cells and micro-lenses might provide a new avenue for development of much-needed drugs to treat human cataract. Full article
(This article belongs to the Special Issue iPS Cells for Disease Modeling)
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16 pages, 701 KiB  
Review
Current Challenges of iPSC-Based Disease Modeling and Therapeutic Implications
by Michael Xavier Doss and Agapios Sachinidis
Cells 2019, 8(5), 403; https://doi.org/10.3390/cells8050403 - 30 Apr 2019
Cited by 272 | Viewed by 21331
Abstract
Induced pluripotent stem cell (iPSC)-based disease modelling and the cell replacement therapy approach have proven to be very powerful and instrumental in biomedical research and personalized regenerative medicine as evidenced in the past decade by unraveling novel pathological mechanisms of a multitude of [...] Read more.
Induced pluripotent stem cell (iPSC)-based disease modelling and the cell replacement therapy approach have proven to be very powerful and instrumental in biomedical research and personalized regenerative medicine as evidenced in the past decade by unraveling novel pathological mechanisms of a multitude of monogenic diseases at the cellular level and the ongoing and emerging clinical trials with iPSC-derived cell products. iPSC-based disease modelling has sparked widespread enthusiasm and has presented an unprecedented opportunity in high throughput drug discovery platforms and safety pharmacology in association with three-dimensional multicellular organoids such as personalized organs-on-chips, gene/base editing, artificial intelligence and high throughput “omics” methodologies. This critical review summarizes the progress made in the past decade with the advent of iPSC discovery in biomedical applications and regenerative medicine with case examples and the current major challenges that need to be addressed to unleash the full potential of iPSCs in clinical settings and pharmacology for more effective and safer regenerative therapy. Full article
(This article belongs to the Special Issue iPS Cells for Disease Modeling)
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