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Stem Cells-From Bench to Bedside 2022
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Stem Cells-From Bench to Bedside 2022

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (20 February 2023) | Viewed by 12282

Special Issue Editor

Prof. Dr. Marcin Majka

E-Mail Website
Guest Editor
Department of Transplantation, Jagiellonian University, Krakow, Poland
Interests: cervical cancer; metabolic reprogramming; metformin; caffeic acid; 5′-adenosine monophosphate-activated protein kinase (AMPK)
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite enormous progress in cardiovascular medicine, many fundamental treatments remain palliative rather than curative, leading to suboptimal clinical outcomes. One such example is heart failure, resulting from loss of contractile myocardial tissue.

The emergence of a new field, regenerative medicine with cell replacement therapy enabling recovery of injured tissues and activation of endogenous processes of tissue repair, opens novel paths and new perspectives for development of curative therapies. In this Special Issue devoted to stem cell-based therapies we will discuss recent breakthroughs both in the areas of basic and translational research and clinical medicine. We aim to depict cutting-edge data on recent progress in understanding stem cells biology in relation to their therapeutic potential, new approaches in tracking and imaging of both stem cells and tissues/organs undergoing regeneration, and data from clinical trials of cell-based therapies. Moreover, the mechanisms of stem cells activity including extracellular vesicle production and potential use will be presented.

Prof. Dr. Marcin Majka
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
  • cell tracking
  • tissue imaging
  • replacement therapy
  • extracellular vesicles

Published Papers (4 papers)

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Research

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13 pages, 2667 KiB  
Article
Antifibrotic TSG-6 Expression Is Synergistically Increased in Both Cells during Coculture of Mesenchymal Stem Cells and Macrophages via the JAK/STAT Signaling Pathway
by Seong Chan Gong, Yongdae Yoon, Pil Young Jung, Moon Young Kim, Soon Koo Baik, Hoon Ryu and Young Woo Eom
Int. J. Mol. Sci. 2022, 23(21), 13122; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232113122 - 28 Oct 2022
Cited by 3 | Viewed by 1850
Abstract
The pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β upregulate TNF-α-stimulated gene 6 (TSG-6); however, current knowledge about the optimal conditions for TSG-6 expression in mesenchymal stem cells (MSCs) is limited. Here, we investigated whether TSG-6 expression varies depending on the polarization [...] Read more.
The pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β upregulate TNF-α-stimulated gene 6 (TSG-6); however, current knowledge about the optimal conditions for TSG-6 expression in mesenchymal stem cells (MSCs) is limited. Here, we investigated whether TSG-6 expression varies depending on the polarization state of macrophages co-cultured with adipose tissue-derived stem cells (ASCs) and analyzed the optimal conditions for TSG-6 expression in ASCs. TSG-6 expression increased in ASCs co-cultured with M0, M1, and M2 macrophages indirectly; among them, M1 macrophages resulted in the highest increase in TSG-6 expression in ASCs. TSG-6 expression in ASCs dramatically increased by combination (but not single) treatment of TNF-α, IL-1β, interferon-gamma (IFN-γ), and lipopolysaccharide (LPS). In addition, phosphorylation of signal transducer and activator of transcription (STAT) 1/3 was observed in response to IFN-γ and LPS treatment but not TNF-α and/or IL-1β. STAT1/3 activation synergistically increased TNF-α/IL-1β-dependent TSG-6 expression, and JAK inhibitors suppressed TSG-6 expression both in ASCs and macrophages. In LX-2 hepatic stellate cells, TSG-6 inhibited TGF-β-induced Smad3 phosphorylation, resulting in decreased α-smooth muscle actin (SMA) expression. Moreover, fibrotic activities of LX-2 cells induced by TGF-β were dramatically decreased after indirect co-culture with ASCs and M1 macrophages. These results suggest that a comprehensive inflammatory microenvironment may play an important role in determining the therapeutic properties of ASCs by increasing TSG-6 expression through STAT1/3 activation. Full article
(This article belongs to the Special Issue Stem Cells-From Bench to Bedside 2022)
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17 pages, 3850 KiB  
Article
An Axis between the Long Non-Coding RNA HOXA11-AS and NQOs Enhances Metastatic Ability in Oral Squamous Cell Carcinoma
by Chie Nakashima, Rina Fujiwara-Tani, Shiori Mori, Shingo Kishi, Hitoshi Ohmori, Kiyomu Fujii, Takuya Mori, Yoshihiro Miyagawa, Kazuhiko Yamamoto, Tadaaki Kirita, Yi Luo and Hiroki Kuniyasu
Int. J. Mol. Sci. 2022, 23(18), 10704; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810704 - 14 Sep 2022
Cited by 6 | Viewed by 1884
Abstract
Long non-coding RNAs (lncRNAs) play critical roles in human cancers. HOXA11 anti-sense RNA (HOXA11-AS) is an lncRNA belonging to the homeobox (HOX) gene cluster that promotes liver metastasis in human colon cancer. However, its role and mechanism of action in human [...] Read more.
Long non-coding RNAs (lncRNAs) play critical roles in human cancers. HOXA11 anti-sense RNA (HOXA11-AS) is an lncRNA belonging to the homeobox (HOX) gene cluster that promotes liver metastasis in human colon cancer. However, its role and mechanism of action in human oral squamous cell carcinoma (OSCC) are unclear. In this study, we investigated HOXA11-AS expression and function in human OSCC tissues and cell lines, as well as a mouse model of OSCC. Our analyses showed that HOXA11-AS expression in human OSCC cases correlates with lymph node metastasis, nicotinamide adenine dinucleotide (NAD)(P)H: quinone oxidoreductase 1 (NQO1) upregulation, and dihydronicotinamide riboside (NRH): quinone oxidoreductase 2 (NQO2) downregulation. Using the human OSCC cell lines HSC3 and HSC4, we demonstrate that HOXA11-AS promotes NQO1 expression by sponging microRNA-494. In contrast, HOXA11-AS recruits zeste homolog 2 (EZH2) to the NQO2 promoter to suppress its expression via the trimethylation of H3K27. The upregulation of NQO1 enzymatic activity by HOXA11-AS results in the consumption of flavin adenine dinucleotide (FAD), which reduces FAD-requiring glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity and suppresses glycolysis. However, our analyses show that lactic acid fermentation levels are preserved by glutaminolysis due to increased malic enzyme-1 expression, promoting enhanced proliferation, invasion, survival, and drug resistance. In contrast, suppression of NQO2 expression reduces the consumption of NRH via NQO2 enzymatic activity and increases NAD levels, which promotes enhanced stemness and metastatic potential. In mouse tumor models, knockdown of HOXA11-AS markedly suppressed tumor growth and lung metastasis. From these findings, targeting HOXA11-AS may strongly suppress high-grade OSCC by regulating both NQO1 and NQO2. Full article
(This article belongs to the Special Issue Stem Cells-From Bench to Bedside 2022)
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Review

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17 pages, 726 KiB  
Review
Are the Properties of Bone Marrow-Derived Mesenchymal Stem Cells Influenced by Overweight and Obesity?
by Qiang Zong, Katrin Bundkirchen, Claudia Neunaber and Sandra Noack
Int. J. Mol. Sci. 2023, 24(5), 4831; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24054831 - 02 Mar 2023
Cited by 7 | Viewed by 1511
Abstract
Bone marrow-derived mesenchymal stem cells (BMSCs) are promising candidates for cell-based therapies. Growing evidence has indicated that overweight/obesity can change the bone marrow microenvironment, which affects some properties of BMSCs. As the overweight/obese population rapidly increases, they will inevitably become a potential source [...] Read more.
Bone marrow-derived mesenchymal stem cells (BMSCs) are promising candidates for cell-based therapies. Growing evidence has indicated that overweight/obesity can change the bone marrow microenvironment, which affects some properties of BMSCs. As the overweight/obese population rapidly increases, they will inevitably become a potential source of BMSCs for clinical application, especially when receiving autologous BMSC transplantation. Given this situation, the quality control of these cells has become particularly important. Therefore, it is urgent to characterize BMSCs isolated from overweight/obese bone marrow environments. In this review, we summarize the evidence of the effects of overweight/obesity on the biological properties of BMSCs derived from humans and animals, including proliferation, clonogenicity, surface antigen expression, senescence, apoptosis, and trilineage differentiation, as well as the underlying mechanisms. Overall, the conclusions of existing studies are not consistent. Most studies demonstrate that overweight/obesity can influence one or more characteristics of BMSCs, while the involved mechanisms are still unclear. Moreover, insufficient evidence proves that weight loss or other interventions can rescue these qualities to baseline status. Thus, further research should address these issues and prioritize developing methods to improve functions of overweight- or obesity-derived BMSCs. Full article
(This article belongs to the Special Issue Stem Cells-From Bench to Bedside 2022)
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17 pages, 616 KiB  
Review
Immunomodulatory Mechanisms of Mesenchymal Stem Cells and Their Potential Clinical Applications
by Yutong Huang, Qiang Wu and Paul Kwong Hang Tam
Int. J. Mol. Sci. 2022, 23(17), 10023; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231710023 - 02 Sep 2022
Cited by 39 | Viewed by 6240
Abstract
Mesenchymal stem cells (MSCs) are multipotent stem cells with the capacity of self-renewal, homing, and low immunogenicity. These distinct biological characteristics have already shown immense potential in regenerative medicine. MSCs also possess immunomodulatory properties that can maintain immune homeostasis when the immune response [...] Read more.
Mesenchymal stem cells (MSCs) are multipotent stem cells with the capacity of self-renewal, homing, and low immunogenicity. These distinct biological characteristics have already shown immense potential in regenerative medicine. MSCs also possess immunomodulatory properties that can maintain immune homeostasis when the immune response is over-activated or under-activated. The secretome of MSCs consists of cytokines, chemokines, signaling molecules, and growth factors, which effectively contribute to the regulation of immune and inflammatory responses. The immunomodulatory effects of MSCs can also be achieved through direct cell contact with microenvironmental factors and immune cells. Furthermore, preconditioned and engineered MSCs can specifically improve the immunomodulation effects in diverse clinical applications. These multifunctional properties of MSCs enable them to be used as a prospective therapeutic strategy to treat immune disorders, including autoimmune diseases and incurable inflammatory diseases. Here we review the recent exploration of immunomodulatory mechanisms of MSCs and briefly discuss the promotion of the genetically engineered MSCs. Additionally, we review the potential clinical applications of MSC-mediated immunomodulation in four types of immune diseases, including systemic lupus erythematosus, Crohn’s disease, graft-versus-host disease, and COVID-19. Full article
(This article belongs to the Special Issue Stem Cells-From Bench to Bedside 2022)
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