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Biomedicines
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Pluripotent Stem Cell: Current Understanding and Future Directions
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Pluripotent Stem Cell: Current Understanding and Future Directions

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 17824

Special Issue Editor

Dr. Aline Yen Ling Wang

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Guest Editor
Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
Interests: induced pluripotent stem cells; mesenchymal stem cells; transplant immunology; autoimmunity; peripheral nerve regeneration; vascularized composite allotransplantation; cell therapy; exosome therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue, “Pluripotent Stem Cells: Current Understanding and Future Directions”, will mainly focus on induced pluripotent stem cells (iPSCs) and potential therapeutic applications of their derivatives.

Induced pluripotent stem cells can be generated by reprogramming somatic cells using the delivery of exogenous pluripotent factors such as  Oct4, Sox2, Nanog, and Klf4. The delivery methods of pluripotent transgenes include genomic integrated strategies, such as lentivirus or retrovirus transduction, and non-genomic integrated strategies such as episomal plasmid transfection, adenovirus transduction, mRNA transfection, or Sendai virus transduction. The overexpression of these pluripotent factors makes the somatic cells undergo transformation into pluripotent stem cells by the obtainment of round morphology, multilineage differentiation abilities, and self-renewal properties. Therefore, iPSCs are similar to embryonic stem cells (ESCs) in that they possess similar regenerative abilities and can differentiate into any cell type in the body, whereas iPSC generation does not face the ethical controversies related to ESC sources. The therapeutic applications of autologous iPSCs have great promise in tissue engineering, regenerative, and personalized medicine. iPSCs-differentiated cells may have the potential to be applied to disease cures or the screening of new drugs. Moreover, allogeneic iPSC-derived exosomes (iPSCs-Exos) act as cell-free therapy and may have broad application prospects in disease treatments.

We invite authors in the field to submit original research or review articles pertaining to this important and fast-progressing field of iPSC-associated medicine.

Dr. Aline Yen Ling Wang
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. Biomedicines 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 2600 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
  • iPSC generation
  • somatic reprogramming
  • iPSC-derived cells
  • cell therapy
  • exosome therapy
  • therapeutic application
  • drug screening

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Related Special Issue

Published Papers (9 papers)

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Research

Jump to: Review

23 pages, 6685 KiB  
Article
Detection of ER Stress in iPSC-Derived Neurons Carrying the p.N370S Mutation in the GBA1 Gene
by Elena S. Yarkova, Elena V. Grigor’eva, Sergey P. Medvedev, Denis A. Tarasevich, Sophia V. Pavlova, Kamila R. Valetdinova, Julia M. Minina, Suren M. Zakian and Anastasia A. Malakhova
Biomedicines 2024, 12(4), 744; https://doi.org/10.3390/biomedicines12040744 - 27 Mar 2024
Viewed by 1964
Abstract
Endoplasmic reticulum (ER) stress is involved in the pathogenesis of many human diseases, such as cancer, type 2 diabetes, kidney disease, atherosclerosis and neurodegenerative diseases, in particular Parkinson’s disease (PD). Since there is currently no treatment for PD, a better understanding of the [...] Read more.
Endoplasmic reticulum (ER) stress is involved in the pathogenesis of many human diseases, such as cancer, type 2 diabetes, kidney disease, atherosclerosis and neurodegenerative diseases, in particular Parkinson’s disease (PD). Since there is currently no treatment for PD, a better understanding of the molecular mechanisms underlying its pathogenesis, including the mechanisms of the switch from adaptation in the form of unfolded protein response (UPR) to apoptosis under ER stress conditions, may help in the search for treatment methods. Genetically encoded biosensors based on fluorescent proteins are suitable tools that facilitate the study of living cells and visualization of molecular events in real time. The combination of technologies to generate patient-specific iPSC lines and genetically encoded biosensors allows the creation of cell models with new properties. Using CRISPR-Cas9-mediated homologous recombination at the AAVS1 locus of iPSC with the genetic variant p.N370S (rs76763715) in the GBA1 gene, we created a cell model designed to study the activation conditions of the IRE1-XBP1 cascade of the UPR system. The cell lines obtained have a doxycycline-dependent expression of the genetically encoded biosensor XBP1-TagRFP, possess all the properties of human pluripotent cells, and can be used to test physical conditions and chemical compounds that affect the development of ER stress, the functioning of the UPR system, and in particular, the IRE1-XBP1 cascade. Full article
(This article belongs to the Special Issue Pluripotent Stem Cell: Current Understanding and Future Directions)
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10 pages, 1282 KiB  
Article
Morphological Signal Processing for Phenotype Recognition of Human Pluripotent Stem Cells Using Machine Learning Methods
by Ekaterina Vedeneeva, Vitaly Gursky, Maria Samsonova and Irina Neganova
Biomedicines 2023, 11(11), 3005; https://doi.org/10.3390/biomedicines11113005 - 9 Nov 2023
Cited by 1 | Viewed by 1251
Abstract
Human pluripotent stem cells have the potential for unlimited proliferation and controlled differentiation into various somatic cells, making them a unique tool for regenerative and personalized medicine. Determining the best clone selection is a challenging problem in this field and requires new sensing [...] Read more.
Human pluripotent stem cells have the potential for unlimited proliferation and controlled differentiation into various somatic cells, making them a unique tool for regenerative and personalized medicine. Determining the best clone selection is a challenging problem in this field and requires new sensing instruments and methods able to automatically assess the state of a growing colony (‘phenotype’) and make decisions about its destiny. One possible solution for such label-free, non-invasive assessment is to make phase-contrast images and/or videos of growing stem cell colonies, process the morphological parameters (‘morphological portrait’, or signal), link this information to the colony phenotype, and initiate an automated protocol for the colony selection. As a step in implementing this strategy, we used machine learning methods to find an effective model for classifying the human pluripotent stem cell colonies of three lines according to their morphological phenotype (‘good’ or ‘bad’), using morphological parameters from the previously published data as predictors. We found that the model using cellular morphological parameters as predictors and artificial neural networks as the classification method produced the best average accuracy of phenotype prediction (67%). When morphological parameters of colonies were used as predictors, logistic regression was the most effective classification method (75% average accuracy). Combining the morphological parameters of cells and colonies resulted in the most effective model, with a 99% average accuracy of phenotype prediction. Random forest was the most efficient classification method for the combined data. We applied feature selection methods and showed that different morphological parameters were important for phenotype recognition via either cellular or colonial parameters. Our results indicate a necessity for retaining both cellular and colonial morphological information for predicting the phenotype and provide an optimal choice for the machine learning method. The classification models reported in this study could be used as a basis for developing and/or improving automated solutions to control the quality of human pluripotent stem cells for medical purposes. Full article
(This article belongs to the Special Issue Pluripotent Stem Cell: Current Understanding and Future Directions)
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14 pages, 2215 KiB  
Article
Exogenous OCT4 and SOX2 Contribution to In Vitro Reprogramming in Cattle
by Lucas Simões Machado, Camila Martins Borges, Marina Amaro de Lima, Juliano Rodrigues Sangalli, Jacinthe Therrien, Laís Vicari de Figueiredo Pessôa, Paulo Fantinato Neto, Felipe Perecin, Lawrence Charles Smith, Flavio Vieira Meirelles and Fabiana Fernandes Bressan
Biomedicines 2023, 11(9), 2577; https://doi.org/10.3390/biomedicines11092577 - 19 Sep 2023
Cited by 2 | Viewed by 1295
Abstract
Mechanisms of cell reprogramming by pluripotency-related transcription factors or nuclear transfer seem to be mediated by similar pathways, and the study of the contribution of OCT4 and SOX2 in both processes may help elucidate the mechanisms responsible for pluripotency. Bovine fibroblasts expressing exogenous [...] Read more.
Mechanisms of cell reprogramming by pluripotency-related transcription factors or nuclear transfer seem to be mediated by similar pathways, and the study of the contribution of OCT4 and SOX2 in both processes may help elucidate the mechanisms responsible for pluripotency. Bovine fibroblasts expressing exogenous OCT4 or SOX2, or both, were analyzed regarding the expression of pluripotency factors and imprinted genes H19 and IGF2R, and used for in vitro reprogramming. The expression of the H19 gene was increased in the control sorted group, and putative iPSC-like cells were obtained when cells were not submitted to cell sorting. When sorted cells expressing OCT4, SOX2, or none (control) were used as donor cells for somatic cell nuclear transfer, fusion rates were 60.0% vs. 64.95% and 70.53% vs. 67.24% for SOX2 vs. control and OCT4 vs. control groups, respectively; cleavage rates were 66.66% vs. 81.68% and 86.47% vs. 85.18%, respectively; blastocyst rates were 33.05% vs. 44.15% and 52.06% vs. 44.78%, respectively. These results show that the production of embryos by NT resulted in similar rates of in vitro developmental competence compared to control cells regardless of different profiles of pluripotency-related gene expression presented by donor cells; however, induced reprogramming was compromised after cell sorting. Full article
(This article belongs to the Special Issue Pluripotent Stem Cell: Current Understanding and Future Directions)
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Review

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23 pages, 1933 KiB  
Review
Timing and Graded BMP Signalling Determines Fate of Neural Crest and Ectodermal Placode Derivatives from Pluripotent Stem Cells
by Keshi Chung, Malvina Millet, Ludivine Rouillon and Azel Zine
Biomedicines 2024, 12(10), 2262; https://doi.org/10.3390/biomedicines12102262 - 4 Oct 2024
Viewed by 887
Abstract
Pluripotent stem cells (PSCs) offer many potential research and clinical benefits due to their ability to differentiate into nearly every cell type in the body. They are often used as model systems to study early stages of ontogenesis to better understand key developmental [...] Read more.
Pluripotent stem cells (PSCs) offer many potential research and clinical benefits due to their ability to differentiate into nearly every cell type in the body. They are often used as model systems to study early stages of ontogenesis to better understand key developmental pathways, as well as for drug screening. However, in order to fully realise the potential of PSCs and their translational applications, a deeper understanding of developmental pathways, especially in humans, is required. Several signalling molecules play important roles during development and are required for proper differentiation of PSCs. The concentration and timing of signal activation are important, with perturbations resulting in improper development and/or pathology. Bone morphogenetic proteins (BMPs) are one such key group of signalling molecules involved in the specification and differentiation of various cell types and tissues in the human body, including those related to tooth and otic development. In this review, we describe the role of BMP signalling and its regulation, the consequences of BMP dysregulation in disease and differentiation, and how PSCs can be used to investigate the effects of BMP modulation during development, mainly focusing on otic development. Finally, we emphasise the unique role of BMP4 in otic specification and how refined understanding of controlling its regulation could lead to the generation of more robust and reproducible human PSC-derived otic organoids for research and translational applications. Full article
(This article belongs to the Special Issue Pluripotent Stem Cell: Current Understanding and Future Directions)
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11 pages, 1983 KiB  
Review
Neuronal Cell Differentiation of iPSCs for the Clinical Treatment of Neurological Diseases
by Dong-Hun Lee, Eun Chae Lee, Ji young Lee, Man Ryul Lee, Jae-won Shim and Jae Sang Oh
Biomedicines 2024, 12(6), 1350; https://doi.org/10.3390/biomedicines12061350 - 18 Jun 2024
Cited by 1 | Viewed by 1615
Abstract
Current chemical treatments for cerebrovascular disease and neurological disorders have limited efficacy in tissue repair and functional restoration. Induced pluripotent stem cells (iPSCs) present a promising avenue in regenerative medicine for addressing neurological conditions. iPSCs, which are capable of reprogramming adult cells to [...] Read more.
Current chemical treatments for cerebrovascular disease and neurological disorders have limited efficacy in tissue repair and functional restoration. Induced pluripotent stem cells (iPSCs) present a promising avenue in regenerative medicine for addressing neurological conditions. iPSCs, which are capable of reprogramming adult cells to regain pluripotency, offer the potential for patient-specific, personalized therapies. The modulation of molecular mechanisms through specific growth factor inhibition and signaling pathways can direct iPSCs’ differentiation into neural stem cells (NSCs). These include employing bone morphogenetic protein-4 (BMP-4), transforming growth factor-beta (TGFβ), and Sma-and Mad-related protein (SMAD) signaling. iPSC-derived NSCs can subsequently differentiate into various neuron types, each performing distinct functions. Cell transplantation underscores the potential of iPSC-derived NSCs to treat neurodegenerative diseases such as Parkinson’s disease and points to future research directions for optimizing differentiation protocols and enhancing clinical applications. Full article
(This article belongs to the Special Issue Pluripotent Stem Cell: Current Understanding and Future Directions)
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18 pages, 1109 KiB  
Review
Signaling Mechanisms of Stem Cell Therapy for Intervertebral Disc Degeneration
by Xiaotian Du, Kejiong Liang, Shili Ding and Haifei Shi
Biomedicines 2023, 11(9), 2467; https://doi.org/10.3390/biomedicines11092467 - 6 Sep 2023
Cited by 3 | Viewed by 1775
Abstract
Low back pain is the leading cause of disability worldwide. Intervertebral disc degeneration (IDD) is the primary clinical risk factor for low back pain and the pathological cause of disc herniation, spinal stenosis, and spinal deformity. A possible approach to improve the clinical [...] Read more.
Low back pain is the leading cause of disability worldwide. Intervertebral disc degeneration (IDD) is the primary clinical risk factor for low back pain and the pathological cause of disc herniation, spinal stenosis, and spinal deformity. A possible approach to improve the clinical practice of IDD-related diseases is to incorporate biomarkers in diagnosis, therapeutic intervention, and prognosis prediction. IDD pathology is still unclear. Regarding molecular mechanisms, cellular signaling pathways constitute a complex network of signaling pathways that coordinate cell survival, proliferation, differentiation, and metabolism. Recently, stem cells have shown great potential in clinical applications for IDD. In this review, the roles of multiple signaling pathways and related stem cell treatment in IDD are summarized and described. This review seeks to investigate the mechanisms and potential therapeutic effects of stem cells in IDD and identify new therapeutic treatments for IDD-related disorders. Full article
(This article belongs to the Special Issue Pluripotent Stem Cell: Current Understanding and Future Directions)
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20 pages, 968 KiB  
Review
Cell-Based Therapy for Urethral Regeneration: A Narrative Review and Future Perspectives
by Yangwang Jin, Weixin Zhao, Ming Yang, Wenzhuo Fang, Guo Gao, Ying Wang and Qiang Fu
Biomedicines 2023, 11(9), 2366; https://doi.org/10.3390/biomedicines11092366 - 24 Aug 2023
Cited by 5 | Viewed by 2019
Abstract
Urethral stricture is a common urological disease that seriously affects quality of life. Urethroplasty with grafts is the primary treatment, but the autografts used in clinical practice have unavoidable disadvantages, which have contributed to the development of urethral tissue engineering. Using various types [...] Read more.
Urethral stricture is a common urological disease that seriously affects quality of life. Urethroplasty with grafts is the primary treatment, but the autografts used in clinical practice have unavoidable disadvantages, which have contributed to the development of urethral tissue engineering. Using various types of seed cells in combination with biomaterials to construct a tissue-engineered urethra provides a new treatment method to repair long-segment urethral strictures. To date, various cell types have been explored and applied in the field of urethral regeneration. However, no optimal strategy for the source, selection, and application conditions of the cells is available. This review systematically summarizes the use of various cell types in urethral regeneration and their characteristics in recent years and discusses possible future directions of cell-based therapies. Full article
(This article belongs to the Special Issue Pluripotent Stem Cell: Current Understanding and Future Directions)
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24 pages, 1163 KiB  
Review
Progress and Prospects of Gene Editing in Pluripotent Stem Cells
by Zhenwu Zhang, Xinyu Bao and Chao-Po Lin
Biomedicines 2023, 11(8), 2168; https://doi.org/10.3390/biomedicines11082168 - 1 Aug 2023
Cited by 2 | Viewed by 3186
Abstract
Applying programmable nucleases in gene editing has greatly shaped current research in basic biology and clinical translation. Gene editing in human pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), is highly relevant to clinical cell therapy [...] Read more.
Applying programmable nucleases in gene editing has greatly shaped current research in basic biology and clinical translation. Gene editing in human pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), is highly relevant to clinical cell therapy and thus should be examined with particular caution. First, since all mutations in PSCs will be carried to all their progenies, off-target edits of editors will be amplified. Second, due to the hypersensitivity of PSCs to DNA damage, double-strand breaks (DSBs) made by gene editing could lead to low editing efficiency and the enrichment of cell populations with defective genomic safeguards. In this regard, DSB-independent gene editing tools, such as base editors and prime editors, are favored due to their nature to avoid these consequences. With more understanding of the microbial world, new systems, such as Cas-related nucleases, transposons, and recombinases, are also expanding the toolbox for gene editing. In this review, we discuss current applications of programmable nucleases in PSCs for gene editing, the efforts researchers have made to optimize these systems, as well as new tools that can be potentially employed for differentiation modeling and therapeutic applications. Full article
(This article belongs to the Special Issue Pluripotent Stem Cell: Current Understanding and Future Directions)
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18 pages, 1859 KiB  
Review
The Role of ATP-Binding Cassette Proteins in Stem Cell Pluripotency
by Prince Saini, Sharath Anugula and Yick W. Fong
Biomedicines 2023, 11(7), 1868; https://doi.org/10.3390/biomedicines11071868 - 30 Jun 2023
Cited by 1 | Viewed by 1928
Abstract
Pluripotent stem cells (PSCs) are highly proliferative cells that can self-renew indefinitely in vitro. Upon receiving appropriate signals, PSCs undergo differentiation and can generate every cell type in the body. These unique properties of PSCs require specific gene expression patterns that define stem [...] Read more.
Pluripotent stem cells (PSCs) are highly proliferative cells that can self-renew indefinitely in vitro. Upon receiving appropriate signals, PSCs undergo differentiation and can generate every cell type in the body. These unique properties of PSCs require specific gene expression patterns that define stem cell identity and dynamic regulation of intracellular metabolism to support cell growth and cell fate transitions. PSCs are prone to DNA damage due to elevated replicative and transcriptional stress. Therefore, mechanisms to prevent deleterious mutations in PSCs that compromise stem cell function or increase the risk of tumor formation from becoming amplified and propagated to progenitor cells are essential for embryonic development and for using PSCs including induced PSCs (iPSCs) as a cell source for regenerative medicine. In this review, we discuss the role of the ATP-binding cassette (ABC) superfamily in maintaining PSC homeostasis, and propose how their activities can influence cellular signaling and stem cell fate decisions. Finally, we highlight recent discoveries that not all ABC family members perform only canonical metabolite and peptide transport functions in PSCs; rather, they can participate in diverse cellular processes from genome surveillance to gene transcription and mRNA translation, which are likely to maintain the pristine state of PSCs. Full article
(This article belongs to the Special Issue Pluripotent Stem Cell: Current Understanding and Future Directions)
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