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Unique Response of Pluripotent Stem Cells to External Stimuli and...
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Unique Response of Pluripotent Stem Cells to External Stimuli and Stresses

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

Deadline for manuscript submissions: closed (17 November 2024) | Viewed by 8005

Special Issue Editors

Dr. Taku Kaitsuka

E-Mail Website
Guest Editor
School of Pharmacy at Fukuoka, International University of Health and Welfare, Fukuoka 831-8501, Japan
Interests: stem cells; stress response; neuroscience; neurodevelopmental disorders; protein synthesis; gene expression; Trp channels; pancreatic development
Special Issues, Collections and Topics in MDPI journals
Dr. Farzana Hakim

E-Mail Website
Guest Editor
Team Lead Scientist (Analytical Development), Takeda Pharmaceuticals, Cambridge, MA, USA
Interests: stem cell biology; neuroscience; gene therapy; analytical development; CRISPR-Cas9; bioassay development; drug product development; cell therapy
Dr. Mohd. Raeed Jamiruddin

E-Mail Website
Guest Editor
Department of Pharmacy, Brac University, Dhaka 1212, Bangladesh
Interests: cancer biology; stem cells; alternate lengthening of telomeres; gene expression; pancreatic development; protein synthesis; protein drug development
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In pluripotent stem cells (PSCs) as embryonic and induced pluripotent stem cells (iPSCs), characteristics such as epigenetic state, gene expression profiles, and the cellular localization of proteins are quite different from those of differentiated and somatic cells. Due to these differences, the response to external stimuli and stresses such as hypoxic, heat, and oxidative stress and chemicals, as well as ligands of channels and receptors, etc., is also different between PSCs and differentiated cells. For example, PSCs are highly sensitive to proteotoxic stress by MG132, and the levels of stress-responsive transcription factors change during differentiation. Further, the differences in stress response between cancer stem cells and cancer cells is also an attractive research field for the chemotherapies of cancers.

In this Special Issue, we would like to focus on such differences and the mechanism determining how those cells respond differentially to external stimuli. By clarifying them, we can identify the characteristics of stress response of PSCs and set up a differentiation protocol for somatic tissues by considering their properties. Furthermore, this information could be useful for research on the toxicology of chemicals in embryos and on iPSC-derived stress-related disease models, such as neurodegenerative diseases.

In this Special Issue, we invite original research articles and reviews on the following subjects: (1) the molecular mechanism of response to any stresses in stem cells, including pluripotent, multipotent, and cancer stem cells; (2) the implication of stress response in their stemness and differentiation; (3) iPSC-derived stress-related disease models and their disorders of stress response; (4) chemical or environmental toxicology in embryos and embryonic stem cells.

Dr. Taku Kaitsuka
Dr. Farzana Hakim
Dr. Mohd. Raeed Jamiruddin
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

  • stem cells
  • stress response
  • differentiation
  • heat stress
  • hypoxic stress
  • oxidative stress
  • proteotoxic stress

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Published Papers (4 papers)

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Research

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18 pages, 8531 KiB  
Article
Pathological Role of High Sugar in Mitochondrial Respiratory Chain Defect-Augmented Mitochondrial Stress
by Ebrima D. Cham, Tsung-I Peng and Mei-Jie Jou
Biology 2024, 13(8), 639; https://doi.org/10.3390/biology13080639 - 21 Aug 2024
Viewed by 1143
Abstract
According to many research groups, high glucose induces the overproduction of superoxide anions, with reactive oxygen species (ROS) generally being considered the link between high glucose levels and the toxicity seen at cellular levels. Respiratory complex anomalies can lead to the production of [...] Read more.
According to many research groups, high glucose induces the overproduction of superoxide anions, with reactive oxygen species (ROS) generally being considered the link between high glucose levels and the toxicity seen at cellular levels. Respiratory complex anomalies can lead to the production of ROS. Calcium [Ca2+] at physiological levels serves as a second messenger in many physiological functions. Accordingly, mitochondrial calcium [Ca2+]m overload leads to ROS production, which can be lethal to the mitochondria through various mechanisms. F1F0-ATPase (ATP synthase or complex V) is the enzyme responsible for catalyzing the final step of oxidative phosphorylation. This is achieved by F1F0-ATPase coupling the translocation of protons in the mitochondrial intermembrane space and shuttling them to the mitochondrial matrix for ATP synthesis to take place. Mitochondrial complex V T8993G mutation specifically blocks the translocation of protons across the intermembrane space, thereby blocking ATP synthesis and, in turn, leading to Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP) syndrome. This study seeks to explore the possibility of [Ca2+]m overload mediating the pathological roles of high glucose in defective respiratory chain-mediated mitochondrial stress. NARP cybrids are the in vitro experimental models of cells with F1FO-ATPase defects, with these cells harboring 98% of mtDNA T8993G mutations. Their counterparts, 143B osteosarcoma cell lines, are the parental cell lines used for comparison. We observed that NARP cells mediated and enhanced the death of cells (apoptosis) when incubated with hydrogen peroxide (H2O2) and high glucose, as depicted using the MTT assay of cell viability. Furthermore, using fluorescence probe-coupled laser scanning confocal imaging microscopy, NARP cells were found to significantly enable mitochondrial reactive oxygen species (mROS) formation and enhance the depolarization of the mitochondrial membrane potential (ΔΨm). Elucidating the mechanisms of sugar-enhanced toxicity on the mitochondria may, in the future, help to alleviate the symptoms of patients with NARP syndromes and other neurodegenerative diseases. Full article
(This article belongs to the Special Issue Unique Response of Pluripotent Stem Cells to External Stimuli and Stresses)
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Review

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21 pages, 1748 KiB  
Review
The Emerging Role of Induced Pluripotent Stem Cells as Adoptive Cellular Immunotherapeutics
by Vedika Mehra, Jyoti Bikram Chhetri, Samira Ali and Claire Roddie
Biology 2023, 12(11), 1419; https://doi.org/10.3390/biology12111419 - 11 Nov 2023
Cited by 2 | Viewed by 2424
Abstract
Adoptive cell therapy (ACT) has transformed the treatment landscape for cancer and infectious disease through the investigational use of chimeric antigen receptor T-cells (CAR-Ts), tumour-infiltrating lymphocytes (TILs) and viral-specific T-cells (VSTs). Whilst these represent breakthrough treatments, there are subsets of patients who fail [...] Read more.
Adoptive cell therapy (ACT) has transformed the treatment landscape for cancer and infectious disease through the investigational use of chimeric antigen receptor T-cells (CAR-Ts), tumour-infiltrating lymphocytes (TILs) and viral-specific T-cells (VSTs). Whilst these represent breakthrough treatments, there are subsets of patients who fail to respond to autologous ACT products. This is frequently due to impaired patient T-cell function or “fitness” as a consequence of prior treatments and age, and can be exacerbated by complex manufacturing protocols. Further, the manufacture of autologous, patient-specific products is time-consuming, expensive and non-standardised. Induced pluripotent stem cells (iPSCs) as an allogeneic alternative to patient-specific products can potentially overcome the issues outlined above. iPSC technology provides an unlimited source of rejuvenated iPSC-derived T-cells (T-iPSCs) or natural killer (NK) cells (NK-iPSCs), and in the context of the growing field of allogeneic ACT, iPSCs have enormous potential as a platform for generating off-the-shelf, standardised, “fit” therapeutics for patients. In this review, we evaluate current and future applications of iPSC technology in the CAR-T/NK, TIL and VST space. We discuss current and next-generation iPSC manufacturing protocols, and report on current iPSC-based adoptive therapy clinical trials to elucidate the potential of this technology as the future of ACT. Full article
(This article belongs to the Special Issue Unique Response of Pluripotent Stem Cells to External Stimuli and Stresses)
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17 pages, 6827 KiB  
Review
Cancer Stem Cells and Glioblastoma: Time for Innovative Biomarkers of Radio-Resistance?
by Francesco Pasqualetti, Mario Miniati, Alessandra Gonnelli, Giovanni Gadducci, Noemi Giannini, Laura Palagini, Maricia Mancino, Taiusha Fuentes and Fabiola Paiar
Biology 2023, 12(10), 1295; https://doi.org/10.3390/biology12101295 - 28 Sep 2023
Viewed by 1684
Abstract
Despite countless papers in the field of radioresistance, researchers are still far from clearly understanding the mechanisms triggered in glioblastoma. Cancer stem cells (CSC) are important to the growth and spread of cancer, according to many studies. In addition, more recently, it has [...] Read more.
Despite countless papers in the field of radioresistance, researchers are still far from clearly understanding the mechanisms triggered in glioblastoma. Cancer stem cells (CSC) are important to the growth and spread of cancer, according to many studies. In addition, more recently, it has been suggested that CSCs have an impact on glioblastoma patients’ prognosis, tumor aggressiveness, and treatment outcomes. In reviewing this new area of biology, we will provide a summary of the most recent research on CSCs and their role in the response to radio-chemotherapy in GB. In this review, we will examine the radiosensitivity of stem cells. Moreover, we summarize the current knowledge of the biomarkers of stemness and evaluate their potential function in the study of radiosensitivity. Full article
(This article belongs to the Special Issue Unique Response of Pluripotent Stem Cells to External Stimuli and Stresses)
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18 pages, 3071 KiB  
Review
Stress Factors as Possible Regulators of Pluripotent Stem Cell Survival and Differentiation
by Toqa Darwish, Nuha Taysir Swaidan and Mohamed M. Emara
Biology 2023, 12(8), 1119; https://doi.org/10.3390/biology12081119 - 11 Aug 2023
Cited by 2 | Viewed by 1548
Abstract
In recent years, extensive research efforts have been directed toward pluripotent stem cells, primarily due to their remarkable capacity for pluripotency. This unique attribute empowers these cells to undergo self-renewal and differentiate into various cell types originating from the ectoderm, mesoderm, and endoderm [...] Read more.
In recent years, extensive research efforts have been directed toward pluripotent stem cells, primarily due to their remarkable capacity for pluripotency. This unique attribute empowers these cells to undergo self-renewal and differentiate into various cell types originating from the ectoderm, mesoderm, and endoderm germ layers. The delicate balance and precise regulation of self-renewal and differentiation are essential for the survival and functionality of these cells. Notably, exposure to specific environmental stressors can activate numerous transcription factors, initiating a diverse array of stress response pathways. These pathways play pivotal roles in regulating gene expression and protein synthesis, ultimately aiming to preserve cell survival and maintain cellular functions. Reactive oxygen species, heat shock, hypoxia, osmotic stress, DNA damage, endoplasmic reticulum stress, and mechanical stress are among the examples of such stressors. In this review, we comprehensively discuss the impact of environmental stressors on the growth of embryonic cells. Furthermore, we provide a summary of the distinct stress response pathways triggered when pluripotent stem cells are exposed to different environmental stressors. Additionally, we highlight recent discoveries regarding the role of such stressors in the generation, differentiation, and self-renewal of induced pluripotent stem cells. Full article
(This article belongs to the Special Issue Unique Response of Pluripotent Stem Cells to External Stimuli and Stresses)
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