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Mesenchymal Stromal and Immune Cells’ Involvement in Human Diseases and Their Treatment

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

Deadline for manuscript submissions: 20 April 2025 | Viewed by 5058

Special Issue Editor

Dr. Mirjana Jerkic

E-Mail Website
Guest Editor
The Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, Unity Health Toronto, University of Toronto, Toronto, ON M5B 1T8, Canada
Interests: stem cells (and MSCs, in particular); mitochondria; macrophages; brain and lung injury; sepsis; ischemia-reperfusion; TGFβ pathways; translational research and clinical studies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to announce this Special Issue on “Mesenchymal Stromal and Immune Cells’ Involvement in Human Diseases and Their Treatment”. Mesenchymal stromal cells (MSCs) are multipotent cells that have demonstrated promise in various preclinical disease models, including lung injury, sepsis, pneumonia, and cardiovascular diseases. MSCs are also being tested in clinical trials in critically ill patients with sepsis, in the prevention of graft vs. host diseases, acute lung injury, COVID-19 pneumonia, liver cirrhosis, cancer, wound healing problems, etc. Despite extensive research in the field of MSCs, our understanding of their mechanisms of action is incomplete; this Special Issue will advance our understanding in this important research field.

It has been recognized that the interplay between MSCs and immune cells represents one of the key mechanisms by which MSCs exert their therapeutic benefits. MSC interactions include, but are not limited to, monocytes/macrophages, dendritic cells, and T and B cells (especially T and B regulatory cells). MSCs also have the potential to mitigate abnormal autoinflammation in the diseased microenvironment. Recent preclinical studies and clinical trials have demonstrated that the exploration of the mechanisms of MSC–immune cell interplay has tremendous potential in optimizing MSCs’ therapeutic effects.

Therefore, the main scope of this Special Issue is to highlight the current state of knowledge about the molecular mechanisms by which MSCs act in health and disease, especially their modulation of host immune and inflammatory responses. This issue is intended to give further insights into MSCs’ potent paracrine properties, their interaction with the environment, and their involvement in tissue repair, at both local and systemic levels.

We welcome original research and up-to-date review papers. Although, usually, pure clinical research or model studies, survey studies, and correlation research papers would fall outside of the scope of IJMS, we welcome clinical and model submissions featuring biomolecular experiments for this Special Issue.

Dr. Mirjana Jerkić
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

  • MSC homing
  • macrophages
  • lung injury
  • inflammation
  • sepsis
  • COVID-19
  • heart
  • liver
  • cell therapy

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Related Special Issue

Published Papers (4 papers)

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Research

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17 pages, 2454 KiB  
Article
Umbilical Cord Mesenchymal Stem Cell Secretome: A Potential Regulator of B Cells in Systemic Lupus Erythematosus
by Adelina Yordanova, Mariana Ivanova, Kalina Tumangelova-Yuzeir, Alexander Angelov, Stanimir Kyurkchiev, Kalina Belemezova, Ekaterina Kurteva, Dobroslav Kyurkchiev and Ekaterina Ivanova-Todorova
Int. J. Mol. Sci. 2024, 25(23), 12515; https://doi.org/10.3390/ijms252312515 - 21 Nov 2024
Viewed by 205
Abstract
Autoimmune diseases represent a severe personal and healthcare problem that seeks novel therapeutic solutions. Mesenchymal stem cells (MSCs) are multipotent cells with interesting cell biology and promising therapeutic potential. The immunoregulatory effects of secretory factors produced by umbilical cord mesenchymal stem cells (UC-MSCs) [...] Read more.
Autoimmune diseases represent a severe personal and healthcare problem that seeks novel therapeutic solutions. Mesenchymal stem cells (MSCs) are multipotent cells with interesting cell biology and promising therapeutic potential. The immunoregulatory effects of secretory factors produced by umbilical cord mesenchymal stem cells (UC-MSCs) were assessed on B lymphocytes from 17 patients with systemic lupus erythematosus (SLE), as defined by the 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE, and 10 healthy volunteers (HVs). Peripheral blood mononuclear cells (PBMCs) from patients and HVs were cultured in a UC-MSC-conditioned medium (UC-MSCcm) and a control medium. Flow cytometry was used to detect the surface expression of CD80, CD86, BR3, CD40, PD-1, and HLA-DR on CD19+ B cells and assess the percentage of B cells in early and late apoptosis. An enzyme-linked immunosorbent assay (ELISA) quantified the production of BAFF, IDO, and PGE2 in PBMCs and UC-MSCs. Under UC-MSCcm influence, the percentage and mean fluorescence intensity (MFI) of CD19+BR3+ cells were reduced in both SLE patients and HVs. Regarding the effects of the MSC secretome on B cells in lupus patients, we observed a decrease in CD40 MFI and a reduced percentage of CD19+PD-1+ and CD19+HLA-DR+ cells. In contrast, in the B cells of healthy participants, we found an increased percentage of CD19+CD80+ cells and decreased CD80 MFI, along with a decrease in CD40 MFI and the percentage of CD19+PD-1+ cells. The UC-MSCcm had a minimal effect on B-cell apoptosis. The incubation of patients’ PBMCs with the UC-MSCcm increased PGE2 levels compared to the control medium. This study provides new insights into the impact of the MSC secretome on the key molecules involved in B-cell activation and antigen presentation and survival, potentially guiding the development of future SLE treatments. Full article
(This article belongs to the Special Issue Mesenchymal Stromal and Immune Cells’ Involvement in Human Diseases and Their Treatment)
24 pages, 9517 KiB  
Article
Senescence-Associated Alterations in Matrisome of Mesenchymal Stem Cells
by Diana Matveeva, Daria Kashirina, Mariia Ezdakova, Irina Larina, Ludmila Buravkova and Andrey Ratushnyy
Int. J. Mol. Sci. 2024, 25(10), 5332; https://doi.org/10.3390/ijms25105332 - 14 May 2024
Cited by 1 | Viewed by 1413
Abstract
The process of aging is intimately linked to alterations at the tissue and cellular levels. Currently, the role of senescent cells in the tissue microenvironment is still being investigated. Despite common characteristics, different cell populations undergo distinctive morphofunctional changes during senescence. Mesenchymal stem [...] Read more.
The process of aging is intimately linked to alterations at the tissue and cellular levels. Currently, the role of senescent cells in the tissue microenvironment is still being investigated. Despite common characteristics, different cell populations undergo distinctive morphofunctional changes during senescence. Mesenchymal stem cells (MSCs) play a pivotal role in maintaining tissue homeostasis. A multitude of studies have examined alterations in the cytokine profile that determine their regulatory function. The extracellular matrix (ECM) of MSCs is a less studied aspect of their biology. It has been shown to modulate the activity of neighboring cells. Therefore, investigating age-related changes in the MSC matrisome is crucial for understanding the mechanisms of tissue niche ageing. This study conducted a broad proteomic analysis of the matrisome of separated fractions of senescent MSCs, including the ECM, conditioned medium (CM), and cell lysate. This is the first time such an analysis has been conducted. It has been established that there is a shift in production towards regulatory molecules and a significant downregulation of the main structural and adhesion proteins of the ECM, particularly collagens, fibulins, and fibrilins. Additionally, a decrease in the levels of cathepsins, galectins, S100 proteins, and other proteins with cytoprotective, anti-inflammatory, and antifibrotic properties has been observed. However, the level of inflammatory proteins and regulators of profibrotic pathways increases. Additionally, there is an upregulation of proteins that can directly cause prosenescent effects on microenvironmental cells (SERPINE1, THBS1, and GDF15). These changes confirm that senescent MSCs can have a negative impact on other cells in the tissue niche, not only through cytokine signals but also through the remodeled ECM. Full article
(This article belongs to the Special Issue Mesenchymal Stromal and Immune Cells’ Involvement in Human Diseases and Their Treatment)
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Review

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37 pages, 4373 KiB  
Review
The Myofibroblast Fate of Therapeutic Mesenchymal Stromal Cells: Regeneration, Repair, or Despair?
by Fereshteh Sadat Younesi and Boris Hinz
Int. J. Mol. Sci. 2024, 25(16), 8712; https://doi.org/10.3390/ijms25168712 - 9 Aug 2024
Viewed by 1576
Abstract
Mesenchymal stromal cells (MSCs) can be isolated from various tissues of healthy or patient donors to be retransplanted in cell therapies. Because the number of MSCs obtained from biopsies is typically too low for direct clinical application, MSC expansion in cell culture is [...] Read more.
Mesenchymal stromal cells (MSCs) can be isolated from various tissues of healthy or patient donors to be retransplanted in cell therapies. Because the number of MSCs obtained from biopsies is typically too low for direct clinical application, MSC expansion in cell culture is required. However, ex vivo amplification often reduces the desired MSC regenerative potential and enhances undesired traits, such as activation into fibrogenic myofibroblasts. Transiently activated myofibroblasts restore tissue integrity after organ injury by producing and contracting extracellular matrix into scar tissue. In contrast, persistent myofibroblasts cause excessive scarring—called fibrosis—that destroys organ function. In this review, we focus on the relevance and molecular mechanisms of myofibroblast activation upon contact with stiff cell culture plastic or recipient scar tissue, such as hypertrophic scars of large skin burns. We discuss cell mechanoperception mechanisms such as integrins and stretch-activated channels, mechanotransduction through the contractile actin cytoskeleton, and conversion of mechanical signals into transcriptional programs via mechanosensitive co-transcription factors, such as YAP, TAZ, and MRTF. We further elaborate how prolonged mechanical stress can create persistent myofibroblast memory by direct mechanotransduction to the nucleus that can evoke lasting epigenetic modifications at the DNA level, such as histone methylation and acetylation. We conclude by projecting how cell culture mechanics can be modulated to generate MSCs, which epigenetically protected against myofibroblast activation and transport desired regeneration potential to the recipient tissue environment in clinical therapies. Full article
(This article belongs to the Special Issue Mesenchymal Stromal and Immune Cells’ Involvement in Human Diseases and Their Treatment)
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16 pages, 1090 KiB  
Review
Potential Consequences of the Use of Adipose-Derived Stem Cells in the Treatment of Hepatocellular Carcinoma
by Aleksandra Gładyś, Adam Mazurski and Piotr Czekaj
Int. J. Mol. Sci. 2024, 25(14), 7806; https://doi.org/10.3390/ijms25147806 - 17 Jul 2024
Viewed by 1174
Abstract
Hepatocellular carcinoma (HCC) ranks as the most prevalent of primary liver cancers and stands as the third leading cause of cancer-related deaths. Early-stage HCC can be effectively managed with available treatment modalities ranging from invasive techniques, such as liver resection and thermoablation, to [...] Read more.
Hepatocellular carcinoma (HCC) ranks as the most prevalent of primary liver cancers and stands as the third leading cause of cancer-related deaths. Early-stage HCC can be effectively managed with available treatment modalities ranging from invasive techniques, such as liver resection and thermoablation, to systemic therapies primarily employing tyrosine kinase inhibitors. Unfortunately, these interventions take a significant toll on the body, either through physical trauma or the adverse effects of pharmacotherapy. Consequently, there is an understandable drive to develop novel HCC therapies. Adipose-derived stem cells (ADSCs) are a promising therapeutic tool. Their facile extraction process, coupled with the distinctive immunomodulatory capabilities of their secretome, make them an intriguing subject for investigation in both oncology and regenerative medicine. The factors they produce are both enzymes affecting the extracellular matrix (specifically, metalloproteinases and their inhibitors) as well as cytokines and growth factors affecting cell proliferation and invasiveness. So far, the interactions observed with various cancer cell types have not led to clear conclusions. The evidence shows both inhibitory and stimulatory effects on tumor growth. Notably, these effects appear to be dependent on the tumor type, prompting speculation regarding their potential inhibitory impact on HCC. This review briefly synthesizes findings from preclinical and clinical studies examining the effects of ADSCs on cancers, with a specific focus on HCC, and emphasizes the need for further research. Full article
(This article belongs to the Special Issue Mesenchymal Stromal and Immune Cells’ Involvement in Human Diseases and Their Treatment)
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