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Biomedicines
Special Issues
Disease-Focused Research Using Stem Cells
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Disease-Focused Research Using Stem Cells

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

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 17724

Special Issue Editor

Dr. Yohei Hayashi

E-Mail Website
Guest Editor
iPS Cell Advanced Characterization and Development Team BioResource Research Center, RIKEN, Tsukuba, JapanFaculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-0074, Japan
Interests: stem cell biology; regenerative medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

With advances in stem cell technologies, as well as with the recent availability of genome editing technologies, we can generate more complex and phenotypically accurate cellular models based on stem cells. Reprogramming technology, in particular, which can generate iPS (induced pluripotent stem) cells or directly transdifferentiated cells, enables us to recapitulate patients’ symptoms in vitro in cultured cells and/or in vivo in transplanted model animals. This opens new and exciting opportunities for stem cell utilization in early discovery, preclinical and translational research in drug development, and cell therapy.

This Special Issue of Biomedicines focuses on recent advances in disease modeling and regenerative medicine using stem cells. The goal is to demonstrate the conceptual and practical advances in order to expand the applications in this exciting field.

We encourage authors to submit original research and review articles where the focus is on various disease-focused studies using pluripotent stem cells and/or somatic stem cells. Potential topics include, but are not limited to:

  • Stem cell establishment and characterization
  • Development of genome-edited stem cells
  • Development of stem cell culture and handling (e.g., differentiation, sorting, preserving, or mass production) methods
  • Development of novel analysis methods using stem cells
  • Disease modeling using stem cells
  • Drug safety tests and screening using stem cells
  • Demonstration of stem cell transplantation for therapeutic purposes

Dr. Yohei Hayashi
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

  • disease-specific iPS cells
  • disease modeling
  • phenotypic screening
  • safety test
  • mutations
  • genome editing
  • isogenic control cells
  • regenerative medicine
  • cell therapy
  • cell manufacturing

Related Special Issue

Published Papers (6 papers)

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Editorial

Jump to: Research, Review

4 pages, 181 KiB  
Editorial
Disease-Focused Research Using Stem Cells
by Yohei Hayashi and Evgeniia Borisova
Biomedicines 2021, 9(11), 1643; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9111643 - 08 Nov 2021
Viewed by 1332
Abstract
In this Special Issue of Biomedicines on disease-focused research using stem cells, we cover the latest conceptual and practical advances in stem cell-based therapies and disease modeling [...] Full article
(This article belongs to the Special Issue Disease-Focused Research Using Stem Cells)

Research

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13 pages, 10131 KiB  
Article
Authentication of Primary Murine Cell Lines by a Microfluidics-Based Lab-On-Chip System
by Yingfen Hong, Nikita Singh, Stefanos Bamopoulos, Enio Gjerga, Laura K. Schmalbrock, Karl Balabanian, Markus Schick, Ulrich Keller and Matthias Wirth
Biomedicines 2020, 8(12), 590; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8120590 - 09 Dec 2020
Cited by 4 | Viewed by 2780
Abstract
The reliable authentication of cell lines is a prerequisite for the reproducibility and replicability of experiments. A common method of cell line authentication is the fragment length analysis (FLA) of short-tandem repeats (STR) by capillary electrophoresis. However, this technique is not always accessible [...] Read more.
The reliable authentication of cell lines is a prerequisite for the reproducibility and replicability of experiments. A common method of cell line authentication is the fragment length analysis (FLA) of short-tandem repeats (STR) by capillary electrophoresis. However, this technique is not always accessible and is often costly. Using a microfluidic electrophoresis system, we analyzed the quality and integrity of different murine cell lines by STR profiling. As a proof of concept, we isolated and immortalized hematopoietic progenitor cells (HPC) of various genotypes through retroviral transduction of the fusion of the estrogen receptor hormone-binding domain with the coding sequence of HoxB8. Cell lines were maintained in the HPC state with Flt3 ligand (FL) and estrogen treatment and could be characterized upon differentiation. In a validation cohort, we applied this technique on primary mutant Kras-driven pancreatic cancer cell lines, which again allowed for clear discrimination. In summary, our study provides evidence that FLA of STR-amplicons by microfluidic electrophoresis allows for stringent quality control and the tracking of cross-contaminations in both genetically stable HPC lines and cancer cell lines, making it a simple and cost-efficient alternative to traditional capillary electrophoresis. Full article
(This article belongs to the Special Issue Disease-Focused Research Using Stem Cells)
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21 pages, 6061 KiB  
Article
Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes, in Contrast to Adipose Tissue-Derived Stromal Cells, Efficiently Improve Heart Function in Murine Model of Myocardial Infarction
by Jacek Stępniewski, Mateusz Tomczyk, Kalina Andrysiak, Izabela Kraszewska, Alicja Martyniak, Agnieszka Langrzyk, Klaudia Kulik, Ewa Wiśniewska, Mateusz Jeż, Urszula Florczyk-Soluch, Katarzyna Polak, Paulina Podkalicka, Neli Kachamakova-Trojanowska, Alicja Józkowicz, Agnieszka Jaźwa-Kusior and Józef Dulak
Biomedicines 2020, 8(12), 578; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8120578 - 07 Dec 2020
Cited by 20 | Viewed by 2951
Abstract
Cell therapies are extensively tested to restore heart function after myocardial infarction (MI). Survival of any cell type after intracardiac administration, however, may be limited due to unfavorable conditions of damaged tissue. Therefore, the aim of this study was to evaluate the therapeutic [...] Read more.
Cell therapies are extensively tested to restore heart function after myocardial infarction (MI). Survival of any cell type after intracardiac administration, however, may be limited due to unfavorable conditions of damaged tissue. Therefore, the aim of this study was to evaluate the therapeutic effect of adipose-derived stromal cells (ADSCs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) overexpressing either the proangiogenic SDF-1α or anti-inflammatory heme oxygenase-1 (HO-1) in a murine model of MI. ADSCs and hiPSCs were transduced with lentiviral vectors encoding luciferase (Luc), GFP and either HO-1 or SDF-1α. hiPSCs were then differentiated to hiPSC-CMs using small molecules modulating the WNT pathway. Genetically modified ADSCs were firstly administered via intracardiac injection after MI induction in Nude mice. Next, ADSCs-Luc-GFP and genetically modified hiPSC-CMs were injected into the hearts of the more receptive NOD/SCID strain to compare the therapeutic effect of both cell types. Ultrasonography, performed on days 7, 14, 28 and 42, revealed a significant decrease of left ventricular ejection fraction (LVEF) in all MI-induced groups. No improvement of LVEF was observed in ADSC-treated Nude and NOD/SCID mice. In contrast, administration of hiPSC-CMs resulted in a substantial increase of LVEF, occurring between 28 and 42 days after MI, and decreased fibrosis, regardless of genetic modification. Importantly, bioluminescence analysis, as well as immunofluorescent staining, confirmed the presence of hiPSC-CMs in murine tissue. Interestingly, the luminescence signal was strongest in hearts treated with hiPSC-CMs overexpressing HO-1. Performed experiments demonstrate that hiPSC-CMs, unlike ADSCs, are effective in improving heart function after MI. Additionally, long-term evaluation of heart function seems to be crucial for proper assessment of the effect of cell administration. Full article
(This article belongs to the Special Issue Disease-Focused Research Using Stem Cells)
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13 pages, 2387 KiB  
Article
Anti-Inflammatory Effects of M-MSCs in DNCB-Induced Atopic Dermatitis Mice
by Bokyeong Ryu, Jieun Baek, Hana Kim, Ji-Heon Lee, Jin Kim, Young-Hoon Jeong, Seul-Gi Lee, Kyu-Ree Kang, Min-Seok Oh, Eun-Young Kim, C-Yoon Kim and Hyung Min Chung
Biomedicines 2020, 8(10), 439; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8100439 - 21 Oct 2020
Cited by 11 | Viewed by 4036
Abstract
Atopic dermatitis (AD) is an inflammatory skin disease caused by an imbalance between Th1 and Th2 cells. AD patients suffer from pruritus, excessive dryness, red or inflamed skin, and complications such as sleep disturbances and depression. Although there are currently many AD treatments [...] Read more.
Atopic dermatitis (AD) is an inflammatory skin disease caused by an imbalance between Th1 and Th2 cells. AD patients suffer from pruritus, excessive dryness, red or inflamed skin, and complications such as sleep disturbances and depression. Although there are currently many AD treatments available there are insufficient data on their long-term stability and comparative effects. Moreover, they have limitations due to various side effects. Multipotent mesenchymal stem cells (M-MSCs) might have potential for next-generation AD therapies. MSCs are capable of immune function regulation and local inflammatory response inhibition. M-MSCs, derived from human embryonic stem cells (hESC), additionally have a stable supply. In L507 antibody array, M-MSCs generally showed similar tendencies to bone marrow-derived mesenchymal stem cells (BM-MSCs), although the immunoregulatory function of M-MSCs seemed to be superior to BM-MSCs. Based on the characteristics of M-MSCs on immunoregulatory functions, we tested a M-MSC conditioned media concentrate (MCMC) in mice with AD lesions on their dorsal skin. MCMC significantly decreased RNA expression levels of inflammatory cytokines in the mouse dorsal skin. It also suppressed serum IgE levels. In addition, significant histopathologic alleviation was identified. In conclusion, secretions of M-MSCs have the potential to effectively improve AD-related inflammatory lesions. M-MSCs showed potential for use in next-generation AD treatment. Full article
(This article belongs to the Special Issue Disease-Focused Research Using Stem Cells)
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Review

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12 pages, 556 KiB  
Review
iPSCs in Modeling and Therapy of Osteoarthritis
by Maria Csobonyeiova, Stefan Polak, Andreas Nicodemou, Radoslav Zamborsky and Lubos Danisovic
Biomedicines 2021, 9(2), 186; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9020186 - 12 Feb 2021
Cited by 14 | Viewed by 2959
Abstract
Osteoarthritis (OA) belongs to chronic degenerative disorders and is often a leading cause of disability in elderly patients. Typically, OA is manifested by articular cartilage erosion, pain, stiffness, and crepitus. Currently, the treatment options are limited, relying mostly on pharmacological therapy, which is [...] Read more.
Osteoarthritis (OA) belongs to chronic degenerative disorders and is often a leading cause of disability in elderly patients. Typically, OA is manifested by articular cartilage erosion, pain, stiffness, and crepitus. Currently, the treatment options are limited, relying mostly on pharmacological therapy, which is often related to numerous complications. The proper management of the disease is challenging because of the poor regenerative capacity of articular cartilage. During the last decade, cell-based approaches such as implantation of autologous chondrocytes or mesenchymal stem cells (MSCs) have shown promising results. However, the mentioned techniques face their hurdles (cell harvesting, low proliferation capacity). The invention of induced pluripotent stem cells (iPSCs) has created new opportunities to increase the efficacy of the cartilage healing process. iPSCs may represent an unlimited source of chondrocytes derived from a patient’s somatic cells, circumventing ethical and immunological issues. Aside from the regenerative potential of iPSCs, stem cell-derived cartilage tissue models could be a useful tool for studying the pathological process of OA. In our recent article, we reviewed the progress in chondrocyte differentiation techniques, disease modeling, and the current status of iPSC-based regenerative therapy of OA. Full article
(This article belongs to the Special Issue Disease-Focused Research Using Stem Cells)
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33 pages, 2170 KiB  
Review
Efficacy and Mode of Action of Mesenchymal Stem Cells in Non-Ischemic Dilated Cardiomyopathy: A Systematic Review
by Cecilie Hoeeg, Sabina Frljak, Abbas Ali Qayyum, Bojan Vrtovec, Jens Kastrup, Annette Ekblond and Bjarke Follin
Biomedicines 2020, 8(12), 570; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8120570 - 05 Dec 2020
Cited by 10 | Viewed by 3077
Abstract
Non-ischemic dilated cardiomyopathy (NIDCM) constitutes one of the most common causes to non-ischemic heart failure. Despite treatment, the disease often progresses, causing severe morbidity and mortality, making novel treatment strategies necessary. Due to the regenerative actions of mesenchymal stem cells (MSCs), they have [...] Read more.
Non-ischemic dilated cardiomyopathy (NIDCM) constitutes one of the most common causes to non-ischemic heart failure. Despite treatment, the disease often progresses, causing severe morbidity and mortality, making novel treatment strategies necessary. Due to the regenerative actions of mesenchymal stem cells (MSCs), they have been proposed as a treatment for NIDCM. This systematic review aims to evaluate efficacy and mode of action (MoA) of MSC-based therapies in NIDCM. A systematic literature search was conducted in Medline (Pubmed) and Embase. A total of 27 studies were included (3 clinical trials and 24 preclinical studies). MSCs from different tissues and routes of delivery were reported, with bone marrow-derived MSCs and direct intramyocardial injections being the most frequent. All included clinical trials and 22 preclinical trials reported an improvement in cardiac function following MSC treatment. Furthermore, preclinical studies demonstrated alterations in tissue structure, gene, and protein expression patterns, primarily related to fibrosis and angiogenesis. Consequently, MSC treatment can improve cardiac function in NIDCM patients. The MoA underlying this effect involves anti-fibrosis, angiogenesis, immunomodulation, and anti-apoptosis, though these processes seem to be interdependent. These encouraging results calls for larger confirmatory clinical studies, as well as preclinical studies utilizing unbiased investigation of the potential MoA. Full article
(This article belongs to the Special Issue Disease-Focused Research Using Stem Cells)
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