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The Role of Mesenchymal Stem Cells in Organ Repair and Tissue Regeneration

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: 20 October 2025 | Viewed by 2447

Special Issue Editor

Dr. Sara Cruciani

E-Mail Website
Guest Editor
Department of Biomedical Sciences, University of Sassari, Sassari, Italy
Interests: stem cells; cell senescence; stem cell differentiation; gene expression; epigenetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Mesenchymal Stem Cells (MSCs) are multipotent stromal cells with the unique ability to differentiate into various cell types, which can be strongly influenced by epigenetic changes and environmental stimuli. This ability makes MSCs an invaluable resource for repairing damaged tissues and organs in vitro and in vivo. More than 800 clinical trials on humans are related to MSCs as therapy, especially for bone and cartilage defects or neurological disorders. Moreover, MSCs have important immunomodulatory properties, positively influencing the immune system response. Although the exact mechanisms underlying MSC immunomodulation are not entirely understood, it is known that they can move from the resident niche and secrete several soluble factors. Elucidating these mechanisms, enhancing migration, adhesion, and paracrine trophic factor secretion, could pave the way for new therapeutic approaches in regenerative medicine. This Special Issue will include a selection of research papers and reviews to develop accurate strategies for their efficient use in cellular therapy. In addition, clinical studies evaluating epigenetics and stem cells in regenerative medicine are suitable for submission to this Special Issue.

This Special Issue is supervised by Dr. Sara Cruciani and assisted by our Topical Advisory Panel Member, Dr. Giuseppe Garroni (University of Sassari). We welcome your submission.

Dr. Sara Cruciani
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.

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Keywords

  • stem cells
  • differentiation
  • cell therapy
  • tissue regeneration
  • cell mechanisms
  • regenerative medicine
  • immunomodulation

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Published Papers (4 papers)

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Research

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26 pages, 19745 KiB  
Article
Therapeutic Potential of Local and Systemic Adipose-Derived Mesenchymal Stem Cell Injections in a Rat Model of Experimental Periodontitis: Implications for Cardiac Function
by Asmaa Elhaieg, Ahmed Farag, Sai Koung Ngeun, Masahiro Kaneda, Aimi Yokoi, Ahmed S. Mandour and Ryou Tanaka
Int. J. Mol. Sci. 2025, 26(9), 3984; https://doi.org/10.3390/ijms26093984 - 23 Apr 2025
Viewed by 234
Abstract
Periodontitis is a common inflammatory disease that not only damages periodontal tissues but also induces systemic effects, including cardiac dysfunction. Mesenchymal stem cells (MSCs) offer regenerative potential due to their ability to differentiate, modulate immune responses, and secrete anti-inflammatory factors. However, the relative [...] Read more.
Periodontitis is a common inflammatory disease that not only damages periodontal tissues but also induces systemic effects, including cardiac dysfunction. Mesenchymal stem cells (MSCs) offer regenerative potential due to their ability to differentiate, modulate immune responses, and secrete anti-inflammatory factors. However, the relative efficacy of local versus systemic MSC administration remains unclear. This study evaluated the therapeutic effects of adipose-derived MSCs (AD-MSCs) in a rat model of experimental periodontitis, comparing local and systemic administration. AD-MSCs were characterized based on morphology, surface marker expression, and differentiation potential. Ligature-induced periodontitis was established over 60 days, after which AD-MSCs (1 × 106 cells) were administered either supraperiosteally (local group) or intravenously (systemic group). Periodontal regeneration was assessed through clinical, radiographic, and histopathological analyses, while cardiac function was evaluated using echocardiography and histopathological examinations. Results demonstrated that local AD-MSC administration provided superior therapeutic benefits compared to systemic delivery. Locally administered cells significantly enhanced bone regeneration, reduced inflammation, and improved periodontal tissue architecture. In contrast, systemic administration offered moderate benefits but was less effective in restoring periodontal integrity. Similarly, in the heart, local treatment resulted in greater improvements in systolic function, as indicated by enhanced ejection fraction and fractional shortening, along with reduced myocardial fibrosis. Although systemic administration also provided cardioprotective effects, diastolic dysfunction persisted in both treatment groups. In conclusion, local AD-MSC administration proved more effective in regenerating periodontal tissues and mitigating cardiac dysfunction, highlighting its potential as an optimized therapeutic strategy for periodontitis and its systemic complications. Full article
(This article belongs to the Special Issue The Role of Mesenchymal Stem Cells in Organ Repair and Tissue Regeneration)
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15 pages, 6381 KiB  
Article
Piezo1 Ion Channels Regulate the Formation and Spreading of Human Endometrial Mesenchymal Stem Cell Spheroids
by Zuleikha M. Khairullina, Valeria Y. Vasileva and Vladislav I. Chubinskiy-Nadezhdin
Int. J. Mol. Sci. 2025, 26(6), 2474; https://doi.org/10.3390/ijms26062474 - 10 Mar 2025
Viewed by 538
Abstract
Mesenchymal stem cells obtained from desquamated endometrium (eMSCs) are considered as reliable and promising objects for stem cell-based therapy. eMSCs aggregated into three-dimensional (3D) spheroids demonstrate greater efficiency compared to monolayer 2D eMSCs. However, molecular processes and specific mechanisms regulating the effectiveness of [...] Read more.
Mesenchymal stem cells obtained from desquamated endometrium (eMSCs) are considered as reliable and promising objects for stem cell-based therapy. eMSCs aggregated into three-dimensional (3D) spheroids demonstrate greater efficiency compared to monolayer 2D eMSCs. However, molecular processes and specific mechanisms regulating the effectiveness of spheroids remain unknown. Regulation of a number of physiological reactions in MSCs is associated with the functioning of Ca2+-permeable mechanosensitive Piezo1 channels. In our previous study, we showed that selective Piezo1 activation by its selective agonist Yoda1 controls the migratory activity of 2D eMSCs. Here, we aimed to determine the effect of Yoda1 on eMSC spheroid formation and spreading. PIEZO1 mRNA expression was lower in spheroids compared to 2D culture. Spheroids formed with Yoda1 or spread in the presence of Yoda1 demonstrated lower spreading rates compared to control (Yoda1-free) spheroids. The spreading rates of control spheroids depended on the substrate stiffness, whereas spheroids formed with Yoda1 had similar spreading rates regardless of the surface properties. Our results demonstrate several Piezo1-dependent reactions of eMSC spheroids that could be modulated by selective Piezo1 activation. Full article
(This article belongs to the Special Issue The Role of Mesenchymal Stem Cells in Organ Repair and Tissue Regeneration)
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30 pages, 15433 KiB  
Article
Human Liver MSCs Retain Their Basic Cellular Properties in Chronically Inflamed Liver Tissue
by Yan S. Kim, Alexey Yu. Lupatov, Veronika V. Burunova, Nikolay N. Bagmet, Nikita K. Chardarov, Svyatoslav L. Malov, Roman V. Kholodenko, Garnik A. Shatverian, Garik V. Manukyan, Konstantin N. Yarygin and Irina V. Kholodenko
Int. J. Mol. Sci. 2024, 25(24), 13374; https://doi.org/10.3390/ijms252413374 - 13 Dec 2024
Viewed by 866
Abstract
Every 25th death worldwide is associated with liver pathology. The development of novel approaches to liver diseases therapy and protocols for maintaining the vital functions of patients on the liver transplant waiting list are urgently needed. Resident mesenchymal stem cells (MSCs) play a [...] Read more.
Every 25th death worldwide is associated with liver pathology. The development of novel approaches to liver diseases therapy and protocols for maintaining the vital functions of patients on the liver transplant waiting list are urgently needed. Resident mesenchymal stem cells (MSCs) play a significant role in supporting liver tissue integrity and improve the liver condition after infusion. However, it remains unclear whether MSCs isolated from chronically inflamed livers are similar in their basic cellular properties to MSCs obtained from healthy livers. We applied a large array of tests to compare resident MSCs isolated from apparently normal liver tissue and from chronically inflamed livers of patients with fibrosis, cirrhosis, and viral hepatitis. Chronic inflammatory environment did not alter the major cellular characteristics of MSCs, including the expression of MSC markers, stem cell markers, adhesion molecules, and the hallmarks of senescence, as well as cell proliferation, migration, and secretome. Only the expression of some immune checkpoints and toll-like receptors was different. Evidently, MSCs with unchanged cellular properties are present in human liver even at late stages of inflammatory diseases. These cells can be isolated and used as starting material in the development of cell therapies of liver diseases. Full article
(This article belongs to the Special Issue The Role of Mesenchymal Stem Cells in Organ Repair and Tissue Regeneration)
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Review

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18 pages, 3327 KiB  
Review
The Intraosseous Environment: Physiological Parameters, Regulatory Mechanisms, and Emerging Insights in Bone Biology
by Mikhail Yu. Artamonov, Evgeniy L. Sokov, Lyudmila E. Kornilova and Inessa A. Minenko
Int. J. Mol. Sci. 2025, 26(8), 3876; https://doi.org/10.3390/ijms26083876 - 19 Apr 2025
Viewed by 268
Abstract
The intraosseous environment is a dynamic and intricate system integral to bone health, encompassing vascular, cellular, and biochemical interactions that drive key processes such as hematopoiesis, bone remodeling, and systemic mineral regulation. This review examines the structural composition of the bone matrix, the [...] Read more.
The intraosseous environment is a dynamic and intricate system integral to bone health, encompassing vascular, cellular, and biochemical interactions that drive key processes such as hematopoiesis, bone remodeling, and systemic mineral regulation. This review examines the structural composition of the bone matrix, the diverse cellular landscape, and the interconnected vascular and nervous networks, highlighting their roles in preserving bone function and responding to pathological changes. Recent studies reveal regulatory mechanisms involving oxygen tension, ionic balance, signaling molecules, and mechanotransduction pathways that shape bone metabolism and its adaptation to mechanical forces. Insights into the bone microenvironment’s metabolic shifts in cancer and its interaction with inflammation underscore its pivotal role in disease progression and therapeutic innovation. Additionally, advances in imaging techniques and biomaterials fuel progress in bone regeneration and understanding its microenvironment. Exploring the intricate physiochemical dynamics and regulatory networks within the intraosseous system unlocks potential clinical applications in bone diseases, tissue engineering, and systemic metabolic disorders. This comprehensive review bridges fundamental science with translational research, offering insights into the complex yet essential intraosseous environment. Full article
(This article belongs to the Special Issue The Role of Mesenchymal Stem Cells in Organ Repair and Tissue Regeneration)
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