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Mesenchymal Stem/Stromal Cells: Mechanisms and Applications in Tissue Regeneration
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Mesenchymal Stem/Stromal Cells: Mechanisms and Applications in Tissue Regeneration

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 2017

Special Issue Editor

Dr. Daiva Bironaite

E-Mail Website
Guest Editor
Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, LT-08410 Vilnius, Lithuania
Interests: cell death; survival mechanisms; intracellular signaling pathways; oxidative stress; adult human mesenchymal stem/stromal cells; tissue regeneration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Mesenchymal stem/stromal cells (MSCs) have emerged as a cornerstone of regenerative medicine due to their multipotency, immunomodulatory properties, and ability to promote tissue repair. This Special Issue, “Mesenchymal Stem/Stromal Cells: Mechanisms and Applications in Tissue Regeneration”, brings together cutting-edge research and comprehensive reviews on the biology, therapeutic potential, and translational challenges of MSCs. Key topics include the molecular mechanisms underlying MSC differentiation, their interactions with the immune system, and their role in modulating the microenvironment for tissue repair in model systems in vitro and in vivo. The issue also explores innovative approaches for enhancing MSC efficacy, including genetic modifications, biomaterial scaffolds, and extracellular vesicle-based therapies. Additionally, clinical applications in the regeneration of musculoskeletal, cardiovascular, and other tissues are discussed, alongside emerging regulatory and manufacturing considerations. By integrating fundamental insights with translational advancements, this Special Issue provides a holistic perspective on the evolving landscape of MSC-based therapies and their future in regenerative medicine.

Dr. Daiva Bironaite
Guest Editor

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Keywords

  • MSC isolation, identification, and viability
  • MSC differentiation mechanisms
  • extracellular environment modifications
  • intracellular signalling systems
  • cytotoxicity investigations
  • tissue regeneration mechanisms

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Published Papers (3 papers)

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Research

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27 pages, 3715 KB  
Article
Safety and Regenerative Properties of Immortalized Human Mesenchymal Stromal Cell Secretome
by Maxim Karagyaur, Alexandra Primak, Nataliya Basalova, Anna Monakova, Anastasia Tolstoluzhinskaya, Maria Kulebyakina, Elizaveta Chechekhina, Mariya Skryabina, Olga Grigorieva, Vadim Chechekhin, Tatiana Yakovleva, Victoria Turilova, Elena Shagimardanova, Guzel Gazizova, Maksim Vigovskiy, Konstantin Kulebyakin, Veronika Sysoeva, Uliana Dyachkova, Stalik Dzhauari, Kirill Bozov, Vladimir Popov, Zhanna Akopyan, Anastasia Efimenko, Natalia Kalinina and Vsevolod Tkachukadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2025, 26(19), 9322; https://doi.org/10.3390/ijms26199322 - 24 Sep 2025
Viewed by 425
Abstract
The secretome of mesenchymal stromal cells (MSCs) can efficiently stimulate regeneration and therefore is a tempting remedy for “cell-free cellular therapy”. However, the usage of primary MSC cultures as secretome producers for translation studies has obvious obstacles, including the rapid aging of MSC [...] Read more.
The secretome of mesenchymal stromal cells (MSCs) can efficiently stimulate regeneration and therefore is a tempting remedy for “cell-free cellular therapy”. However, the usage of primary MSC cultures as secretome producers for translation studies has obvious obstacles, including the rapid aging of MSC cultures, the need for a large number of verified donors, and donor-to-donor variability of secretome content. MSCs immortalization makes it possible to overcome those limitations and to obtain secretome-producing cultures with a prolonged lifetime. However, the efficacy and safety of such secretomes are critical issues that limit their usage as therapeutic agents. In this study, we tested in large detail how the immortalization of MSC cultures affects the content, biological activity and safety of their secretome. MSCs immortalization via the overexpression of human TERT gene does not significantly alter the qualitative and quantitative composition of their secretome or its activity according to the results of proteomic analysis, ELISA, qPCR and functional tests in vitro. Moreover, we have demonstrated that the secretome of immortalized MSCs does not contain detectable amounts of telomerase and does not possess any transforming activity. Altogether, our data suggest that immortalized MSC cultures may become a reliable source for obtaining standardized active secretome in large-scale quantities for clinical use. Full article
(This article belongs to the Special Issue Mesenchymal Stem/Stromal Cells: Mechanisms and Applications in Tissue Regeneration)
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15 pages, 3236 KB  
Article
Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Alleviated the Inflammatory Response in Mice Infected with the Influenza Virus A (H1N1)
by Hui Xiao, Xiao Yu, Yiding Dong, Shilong Bao, Xiaoting Meng, Jia Zhao and Zhiyong Dong
Int. J. Mol. Sci. 2025, 26(18), 8839; https://doi.org/10.3390/ijms26188839 - 11 Sep 2025
Viewed by 525
Abstract
Influenza A virus (H1N1) infection poses a significant global public health challenge and imposes a substantial economic burden. Numerous studies have shown that excessive immune activation and dysregulated inflammatory responses following influenza virus infection are the primary causes of disease progression and mortality. [...] Read more.
Influenza A virus (H1N1) infection poses a significant global public health challenge and imposes a substantial economic burden. Numerous studies have shown that excessive immune activation and dysregulated inflammatory responses following influenza virus infection are the primary causes of disease progression and mortality. Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) exhibit potent anti-inflammatory effects. Therefore, this study aims to investigate the effects of extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUCMSC-EVs) on pulmonary inflammatory responses in mice infected with the influenza A virus (H1N1). The study first established a mouse influenza virus infection model by intranasal inoculation of the influenza A virus (H1N1), followed by treatment with hUCMSC-EVs (70 μg) administered via tail vein injection for four consecutive days. The results showed that compared with the H1N1 group, after treatment with hUCMSC-EVs, pulmonary edema was reduced, inflammatory cell infiltration in the lungs was significantly decreased, and the expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) proteins in serum and lung tissue were significantly reduced. Therefore, this study suggests that the protective effect of hUCMSC-EVs against lung damage caused by influenza A virus (H1N1) infection may be related to the reduction in inflammatory cytokine levels of TNF-α, IL-1β, and IL-6, thereby alleviating pulmonary inflammation. Full article
(This article belongs to the Special Issue Mesenchymal Stem/Stromal Cells: Mechanisms and Applications in Tissue Regeneration)
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Review

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35 pages, 1409 KB  
Review
Ex Vivo Preconditioning as a Useful Tool for Modification of the Extracellular Matrix of Multipotent Mesenchymal Stromal Cells
by Elena Andreeva, Olga Zhidkova, Diana Matveeva, Aleksandra Gornostaeva, Margarita Lobanova and Ludmila Buravkova
Int. J. Mol. Sci. 2025, 26(13), 6301; https://doi.org/10.3390/ijms26136301 - 30 Jun 2025
Viewed by 720
Abstract
Cell technologies have provided promising tools for modulating the properties of multipotent mesenchymal stem/stromal cells (MSCs) to meet the needs of cell therapy as well as tissue engineering and regenerative medicine (TERM). Ex vivo preconditioning is directed at enhancing the engraftment of MSCs [...] Read more.
Cell technologies have provided promising tools for modulating the properties of multipotent mesenchymal stem/stromal cells (MSCs) to meet the needs of cell therapy as well as tissue engineering and regenerative medicine (TERM). Ex vivo preconditioning is directed at enhancing the engraftment of MSCs and activating their secretory activity, primarily the production of soluble mediators. The present review aims to highlight the underestimated effect of the most accepted preconditioning approaches on the modification of the important set of insoluble molecules secreted by MSCs into extracellular space—the extracellular matrix (ECM). A thorough review of the published literature was performed, with particular emphasis on ECM-related data. The analysis of data on ECM changes showed that most of the applied preconditioning methods—hypoxia, inflammatory priming, pharmacological agents, 3D culture, and scaffolds—generally stimulate ECM production, increase the deposition of growth factors, promote alignment, and increase ECM stiffness. There are already preliminary results demonstrating the successful application of preconditioned ECM for promoting angiogenesis, targeted stromal lineage differentiation, and other therapeutic goals. The prospects for further research in this area are discussed. Full article
(This article belongs to the Special Issue Mesenchymal Stem/Stromal Cells: Mechanisms and Applications in Tissue Regeneration)
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