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Stem Cell Research: Discovering the Mechanistic Understanding for Therapeutic Application
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Stem Cell Research: Discovering the Mechanistic Understanding for Therapeutic Application

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

Deadline for manuscript submissions: closed (20 April 2025) | Viewed by 12360

Special Issue Editor

Dr. Rachel A. Oldershaw

E-Mail Website
Guest Editor
Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK
Interests: osteoarthritis; cartilage; rheumatology; biological therapy

Special Issue Information

Dear Colleagues, 

Stem cells have become a cornerstone of emerging regenerative medicine strategies, aiming to utilize tissue repair to restore function to cells damaged as a result of injury, ageing or disease. There is, therefore, a critical need to strengthen our understanding of the underpinning biological mechanisms and pathways that determine how these regenerative cells self-renew and differentiate, with the aim of optimizing protocols for maximal therapeutic efficacy and supporting the definition of product specification for regulatory approvals. This Special Issue aims to address unresolved problems in the therapeutic application of stem cells at the molecular, cellular, tissue, organ and system levels, seeking to advance existing techniques and determine novel ways of determining how stem cells can be used within the field of regenerative medicine.

This Special Issue welcomes original research articles, reviews, methods and other article types focusing on (but not limited to) the following areas:

  • Mechanisms of pluripotency/multipotency and self-renewal;
  • Mechanisms of cell lineage differentiation and the determination of therapeutic function;
  • Advanced culture methods for the scale-up and production of therapeutic products;
  • Bioengineering, including the combination of stem cells with biomaterials;
  • Preclinical studies investigating stem cell safety and efficacy;
  • Investigational studies of stem cell safety and efficacy in clinic.

Dr. Rachel A. Oldershaw
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

  • pluripotent stem cells
  • adult stem cells
  • bioengineering
  • regenerative medicine
  • cell therapy

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (3 papers)

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Research

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16 pages, 2562 KiB  
Article
Immunophenotypical Characterization of Limbal Mesenchymal Stromal Cell Subsets during In Vitro Expansion
by Sara Aghazadeh, Qiuyue Peng, Fereshteh Dardmeh, Jesper Østergaard Hjortdal, Vladimir Zachar and Hiva Alipour
Int. J. Mol. Sci. 2024, 25(16), 8684; https://doi.org/10.3390/ijms25168684 - 9 Aug 2024
Viewed by 1340
Abstract
Limbal mesenchymal stromal cells (LMSCs) reside in the limbal niche, supporting corneal integrity and facilitating regeneration. While mesenchymal stem/stromal cells (MSCs) are used in regenerative therapies, there is limited knowledge about LMSC subpopulations and their characteristics. This study characterized human LMSC subpopulations through [...] Read more.
Limbal mesenchymal stromal cells (LMSCs) reside in the limbal niche, supporting corneal integrity and facilitating regeneration. While mesenchymal stem/stromal cells (MSCs) are used in regenerative therapies, there is limited knowledge about LMSC subpopulations and their characteristics. This study characterized human LMSC subpopulations through the flow cytometric assessment of fifteen cell surface markers, including MSC, wound healing, immune regulation, ASC, endothelial, and differentiation markers. Primary LMSCs were established from remnant human corneal transplant specimens and passaged eight times to observe changes during subculture. The results showed the consistent expression of typical MSC markers and distinct subpopulations with the passage-dependent expression of wound healing, immune regulation, and differentiation markers. High CD166 and CD248 expressions indicated a crucial role in ocular surface repair. CD29 expression suggested an immunoregulatory role. Comparable pigment-epithelial-derived factor (PEDF) expression supported anti-inflammatory and anti-angiogenic roles. Sustained CD201 expression indicated maintained differentiation capability, while VEGFR2 expression suggested potential endothelial differentiation. LMSCs showed higher VEGF expression than fibroblasts and endothelial cells, suggesting a potential contribution to ocular surface regeneration through the modulation of angiogenesis and inflammation. These findings highlight the heterogeneity and multipotent potential of LMSC subpopulations during in vitro expansion, informing the development of standardized protocols for regenerative therapies and improving treatments for ocular surface disorders. Full article
(This article belongs to the Special Issue Stem Cell Research: Discovering the Mechanistic Understanding for Therapeutic Application)
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13 pages, 3010 KiB  
Article
BMP-2 Genome-Edited Human MSCs Protect against Cartilage Degeneration via Suppression of IL-34 in Collagen-Induced Arthritis
by Dong-Sik Chae, Seongho Han, Min-Kyung Lee and Sung-Whan Kim
Int. J. Mol. Sci. 2023, 24(9), 8223; https://doi.org/10.3390/ijms24098223 - 4 May 2023
Cited by 4 | Viewed by 2099
Abstract
Even though the regenerative potential of mesenchymal stem cells (MSCs) has been extensively studied, there is a debate regarding their minimal therapeutic properties. Bone morphogenetic proteins (BMP) are involved in cartilage metabolism, chondrogenesis, and bone healing. In this study, we aimed to analyze [...] Read more.
Even though the regenerative potential of mesenchymal stem cells (MSCs) has been extensively studied, there is a debate regarding their minimal therapeutic properties. Bone morphogenetic proteins (BMP) are involved in cartilage metabolism, chondrogenesis, and bone healing. In this study, we aimed to analyze the role of genome-edited BMP-2 overexpressing amniotic mesenchymal stem cells (AMMs) in a mouse model of collagen-induced arthritis (CIA). The BMP-2 gene was synthesized and inserted into AMMs using transcription activator-like effector nucleases (TALENs), and BMP-2-overexpressing AMMs (AMM/B) were sorted and characterized using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The co-culture of AMM/B with tumor necrosis factor (TNF)-α-treated synovial fibroblasts significantly decreased the levels of interleukin (IL)-34. The therapeutic properties of AMM/B were evaluated using the CIA mouse model. The injection of AMM/B attenuated CIA progression and inhibited T helper (Th)17 cell activation in CIA mice. In addition, the AMM/B injection increased proteoglycan expression in cartilage and decreased the infiltration of inflammatory cells and factors, including IL-1β, TNF-α, cyclooxygenase (COX)-2, and Nuclear factor kappa B (NF-kB) in the joint tissues. Therefore, editing the BMP-2 genome in MSCs might be an alternative strategy to enhance their therapeutic potential for treating cartilage degeneration in arthritic joints. Full article
(This article belongs to the Special Issue Stem Cell Research: Discovering the Mechanistic Understanding for Therapeutic Application)
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Review

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37 pages, 959 KiB  
Review
Mesenchymal Stem Cells in the Pathogenesis and Therapy of Autoimmune and Autoinflammatory Diseases
by Lina N. Zaripova, Angela Midgley, Stephen E. Christmas, Michael W. Beresford, Clare Pain, Eileen M. Baildam and Rachel A. Oldershaw
Int. J. Mol. Sci. 2023, 24(22), 16040; https://doi.org/10.3390/ijms242216040 - 7 Nov 2023
Cited by 25 | Viewed by 8085
Abstract
Mesenchymal stem cells (MSCs) modulate immune responses and maintain self-tolerance. Their trophic activities and regenerative properties make them potential immunosuppressants for treating autoimmune and autoinflammatory diseases. MSCs are drawn to sites of injury and inflammation where they can both reduce inflammation and contribute [...] Read more.
Mesenchymal stem cells (MSCs) modulate immune responses and maintain self-tolerance. Their trophic activities and regenerative properties make them potential immunosuppressants for treating autoimmune and autoinflammatory diseases. MSCs are drawn to sites of injury and inflammation where they can both reduce inflammation and contribute to tissue regeneration. An increased understanding of the role of MSCs in the development and progression of autoimmune disorders has revealed that MSCs are passive targets in the inflammatory process, becoming impaired by it and exhibiting loss of immunomodulatory activity. MSCs have been considered as potential novel cell therapies for severe autoimmune and autoinflammatory diseases, which at present have only disease modifying rather than curative treatment options. MSCs are emerging as potential therapies for severe autoimmune and autoinflammatory diseases. Clinical application of MSCs in rare cases of severe disease in which other existing treatment modalities have failed, have demonstrated potential use in treating multiple diseases, including rheumatoid arthritis, systemic lupus erythematosus, myocardial infarction, liver cirrhosis, spinal cord injury, multiple sclerosis, and COVID-19 pneumonia. This review explores the biological mechanisms behind the role of MSCs in autoimmune and autoinflammatory diseases. It also covers their immunomodulatory capabilities, potential therapeutic applications, and the challenges and risks associated with MSC therapy. Full article
(This article belongs to the Special Issue Stem Cell Research: Discovering the Mechanistic Understanding for Therapeutic Application)
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