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Biology
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Pluripotent Stem Cells, Cell Reprogramming and Tissue Modelling
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Pluripotent Stem Cells, Cell Reprogramming and Tissue Modelling

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

Deadline for manuscript submissions: closed (1 July 2021) | Viewed by 34505

Special Issue Editors

Prof. Dr. Silvia Parisi

E-Mail Website
Guest Editor
Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Via Pansini 5, 80131 Naples, Italy
Interests: pluripotent stem cells; gene expression regulation; disease modelling; chromatin organization; RNA binding protein
Dr. Paul Wieringa

E-Mail Website
Guest Editor
Institute for Technology-Inspired Regenerative Medicine (MERLN)/FHML, Maastricht University, Universiteitssingel 40, 6229 ET Maastricht, The Netherlands
Interests: neural engineering; 3D in vitro platforms; biomedical sciences
Dr. Massimiliano Caiazzo

E-Mail Website
Guest Editor
Department of Molecular Medicine and Medical Biotechnology, University of Naples, “Federico II”, Via Pansini 5, 80131 Naples, Italy
Interests: cell reprogramming; disease modeling
Dr. Fabiana Passaro

E-Mail Website
Guest Editor
University of Naples, “Federico II”, Naples, Italy
Interests: regenerative medicine; cardiac regeneration; direct reprogramming; molecular biology of regeneration

Special Issue Information

Dear Colleagues,

The derivation of embryonic stem cells (ESC), followed by the generation of induced pluripotent stem cells (iPSC) and the possibility of changing the identity of a somatic cell to another type of somatic cell through cell reprogramming, has profoundly changed developmental biology, as well as biomedical research. First, the use of pluripotent stem cells (PSCs), both ESCs and iPSCs, is fundamental for studying molecular mechanisms underlying embryo development, and this is particularly relevant if we use human iPSC differentiation to acquire knowledge on human development. Second, human PSCs, as well as direct reprogramming, hold tremendous potential for disease modeling, drug discovery, predictive toxicology, and regenerative medicine applications, providing access to cell types that are otherwise impossible to acquire. However, to properly use these powerful systems for all these aims, we need profound and complete knowledge of the mechanisms that allow cell reprogramming and guide PSC fate. Moreover, it is necessary to increasingly develop precise and reproducible methods, and to govern the reprogramming and/or the differentiation toward a specific cell fate. The use of biomaterials, as well as organ-on-chip and bio-printing approaches, can really make the difference in generating physiological and pathological tissue models in vitro.

This Special Issue aims to cover recent progresses done in understanding cell reprogramming, PSC differentiation and the use of PSCs, to model tissue physiology and pathology. We will especially focus on recently developed approaches, such as organ-on-chip and organoids that allow a better understanding of tissue function, organization, etc., beyond the single cell level.

We welcome the submission of original research, short communications, and review manuscripts focusing on methods which improve cell reprogramming and the differentiation of PSCs, as well as tissue modelling. Other important aspects that we would like to point out in this Special Issue are the molecular mechanisms that guide cell reprogramming and cell differentiation from PSCs, and those factors that limit the efficiency of these processes.

Prof. Dr. Silvia Parisi
Dr. Paul Wieringa
Dr. Massimiliano Caiazzo
Dr. Fabiana Passaro
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. Biology is an international peer-reviewed open access monthly 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

  • pluripotent stem cell
  • reprogramming
  • transdifferentiation
  • gene control of pluripotency and differentiation
  • regenerative medicine
  • modelling of functional tissues and disease

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Published Papers (5 papers)

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Research

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24 pages, 9842 KiB  
Article
Human Trisomic iPSCs from Down Syndrome Fibroblasts Manifest Mitochondrial Alterations Early during Neuronal Differentiation
by Nunzia Mollo, Matteo Esposito, Miriam Aurilia, Roberta Scognamiglio, Rossella Accarino, Ferdinando Bonfiglio, Rita Cicatiello, Maria Charalambous, Claudio Procaccini, Teresa Micillo, Rita Genesio, Gaetano Calì, Agnese Secondo, Simona Paladino, Giuseppe Matarese, Gabriella De Vita, Anna Conti, Lucio Nitsch and Antonella Izzo
Biology 2021, 10(7), 609; https://doi.org/10.3390/biology10070609 - 30 Jun 2021
Cited by 15 | Viewed by 5118
Abstract
Background: The presence of mitochondrial alterations in Down syndrome suggests that it might affect neuronal differentiation. We established a model of trisomic iPSCs, differentiating into neural precursor cells (NPCs) to monitor the occurrence of differentiation defects and mitochondrial dysfunction. Methods: Isogenic trisomic and [...] Read more.
Background: The presence of mitochondrial alterations in Down syndrome suggests that it might affect neuronal differentiation. We established a model of trisomic iPSCs, differentiating into neural precursor cells (NPCs) to monitor the occurrence of differentiation defects and mitochondrial dysfunction. Methods: Isogenic trisomic and euploid iPSCs were differentiated into NPCs in monolayer cultures using the dual-SMAD inhibition protocol. Expression of pluripotency and neural differentiation genes was assessed by qRT-PCR and immunofluorescence. Meta-analysis of expression data was performed on iPSCs. Mitochondrial Ca2+, reactive oxygen species (ROS) and ATP production were investigated using fluorescent probes. Oxygen consumption rate (OCR) was determined by Seahorse Analyzer. Results: NPCs at day 7 of induction uniformly expressed the differentiation markers PAX6, SOX2 and NESTIN but not the stemness marker OCT4. At day 21, trisomic NPCs expressed higher levels of typical glial differentiation genes. Expression profiles indicated that mitochondrial genes were dysregulated in trisomic iPSCs. Trisomic NPCs showed altered mitochondrial Ca2+, reduced OCR and ATP synthesis, and elevated ROS production. Conclusions: Human trisomic iPSCs can be rapidly and efficiently differentiated into NPC monolayers. The trisomic NPCs obtained exhibit greater glial-like differentiation potential than their euploid counterparts and manifest mitochondrial dysfunction as early as day 7 of neuronal differentiation. Full article
(This article belongs to the Special Issue Pluripotent Stem Cells, Cell Reprogramming and Tissue Modelling)
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19 pages, 3503 KiB  
Article
Inhibition of FGF and TGF-β Pathways in hESCs Identify STOX2 as a Novel SMAD2/4 Cofactor
by Peter F. Renz, Daniel Spies, Panagiota Tsikrika, Anton Wutz, Tobias A. Beyer and Constance Ciaudo
Biology 2020, 9(12), 470; https://doi.org/10.3390/biology9120470 - 16 Dec 2020
Cited by 3 | Viewed by 5162
Abstract
The fibroblast growth factor (FGF) and the transforming growth factor-β (TGF-β) pathways are both involved in the maintenance of human embryonic stem cells (hESCs) and regulate the onset of their differentiation. Their converging functions have suggested that these pathways might share a wide [...] Read more.
The fibroblast growth factor (FGF) and the transforming growth factor-β (TGF-β) pathways are both involved in the maintenance of human embryonic stem cells (hESCs) and regulate the onset of their differentiation. Their converging functions have suggested that these pathways might share a wide range of overlapping targets. Published studies have focused on the long-term effects (24–48 h) of FGF and TGF-β inhibition in hESCs, identifying direct and indirect target genes. In this study, we focused on the earliest transcriptome changes occurring between 3 and 9 h after FGF and TGF-β inhibition to identify direct target genes only. Our analysis clearly shows that only a handful of target transcripts are common to both pathways. This is surprising in light of the previous literature, and has implications for models of cell signaling in human pluripotent cells. In addition, we identified STOX2 as a novel primary target of the TGF-β signaling pathway. We show that STOX2 might act as a novel SMAD2/4 cofactor. Taken together, our results provide insights into the effect of cell signaling on the transcription profile of human pluripotent cells Full article
(This article belongs to the Special Issue Pluripotent Stem Cells, Cell Reprogramming and Tissue Modelling)
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Review

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13 pages, 1101 KiB  
Review
Liver Organoids: Updates on Disease Modeling and Biomedical Applications
by Carmen Caiazza, Silvia Parisi and Massimiliano Caiazzo
Biology 2021, 10(9), 835; https://doi.org/10.3390/biology10090835 - 27 Aug 2021
Cited by 19 | Viewed by 7563
Abstract
Liver organoids are stem cell-derived 3D structures that are generated by liver differentiation signals in the presence of a supporting extracellular matrix. Liver organoids overcome low complexity grade of bidimensional culture and high costs of in vivo models thus representing a turning point [...] Read more.
Liver organoids are stem cell-derived 3D structures that are generated by liver differentiation signals in the presence of a supporting extracellular matrix. Liver organoids overcome low complexity grade of bidimensional culture and high costs of in vivo models thus representing a turning point for studying liver disease modeling. Liver organoids can be established from different sources as induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), hepatoblasts and tissue-derived cells. This novel in vitro system represents an innovative tool to deeper understand the physiology and pathological mechanisms affecting the liver. In this review, we discuss the current advances in the field focusing on their application in modeling diseases, regenerative medicine and drug discovery. Full article
(This article belongs to the Special Issue Pluripotent Stem Cells, Cell Reprogramming and Tissue Modelling)
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23 pages, 1712 KiB  
Review
Brain Organoids: Filling the Need for a Human Model of Neurological Disorder
by Philip Jalink and Massimiliano Caiazzo
Biology 2021, 10(8), 740; https://doi.org/10.3390/biology10080740 - 2 Aug 2021
Cited by 18 | Viewed by 10280
Abstract
Neurological disorders are among the leading causes of death worldwide, accounting for almost all onsets of dementia in the elderly, and are known to negatively affect motor ability, mental and cognitive performance, as well as overall wellbeing and happiness. Currently, most neurological disorders [...] Read more.
Neurological disorders are among the leading causes of death worldwide, accounting for almost all onsets of dementia in the elderly, and are known to negatively affect motor ability, mental and cognitive performance, as well as overall wellbeing and happiness. Currently, most neurological disorders go untreated due to a lack of viable treatment options. The reason for this lack of options is s poor understanding of the disorders, primarily due to research models that do not translate well into the human in vivo system. Current models for researching neurological disorders, neurodevelopment, and drug interactions in the central nervous system include in vitro monolayer cell cultures, and in vivo animal models. These models have shortcomings when it comes to translating research about disorder pathology, development, and treatment to humans. Brain organoids are three-dimensional (3D) cultures of stem cell-derived neural cells that mimic the development of the in vivo human brain with high degrees of accuracy. Researchers have started developing these miniature brains to model neurodevelopment, and neuropathology. Brain organoids have been used to model a wide range of neurological disorders, including the complex and poorly understood neurodevelopmental and neurodegenerative disorders. In this review, we discuss the brain organoid technology, placing special focus on the different brain organoid models that have been developed, discussing their strengths, weaknesses, and uses in neurological disease modeling. Full article
(This article belongs to the Special Issue Pluripotent Stem Cells, Cell Reprogramming and Tissue Modelling)
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26 pages, 9600 KiB  
Review
Fluorescent PSC-Derived Cardiomyocyte Reporter Lines: Generation Approaches and Their Applications in Cardiovascular Medicine
by Naeramit Sontayananon, Charles Redwood, Benjamin Davies and Katja Gehmlich
Biology 2020, 9(11), 402; https://doi.org/10.3390/biology9110402 - 16 Nov 2020
Cited by 2 | Viewed by 5399
Abstract
Recent advances have made pluripotent stem cell (PSC)-derived cardiomyocytes an attractive option to model both normal and diseased cardiac function at the single-cell level. However, in vitro differentiation yields heterogeneous populations of cardiomyocytes and other cell types, potentially confounding phenotypic analyses. Fluorescent PSC-derived [...] Read more.
Recent advances have made pluripotent stem cell (PSC)-derived cardiomyocytes an attractive option to model both normal and diseased cardiac function at the single-cell level. However, in vitro differentiation yields heterogeneous populations of cardiomyocytes and other cell types, potentially confounding phenotypic analyses. Fluorescent PSC-derived cardiomyocyte reporter systems allow specific cell lineages to be labelled, facilitating cell isolation for downstream applications including drug testing, disease modelling and cardiac regeneration. In this review, the different genetic strategies used to generate such reporter lines are presented with an emphasis on their relative technical advantages and disadvantages. Next, we explore how the fluorescent reporter lines have provided insights into cardiac development and cardiomyocyte physiology. Finally, we discuss how exciting new approaches using PSC-derived cardiomyocyte reporter lines are contributing to progress in cardiac cell therapy with respect to both graft adaptation and clinical safety. Full article
(This article belongs to the Special Issue Pluripotent Stem Cells, Cell Reprogramming and Tissue Modelling)
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