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Latest Research on Mesenchymal Stem Cells (2nd Edition)

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: 31 October 2026 | Viewed by 1886

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Pathophysiology Discipline, Faculty of Dental Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
Interests: cellular and molecular mechanisms of stress; apoptosis and inflammation
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Dear Colleagues,

MSCs (mesenchymal stem/stromal cells) are found in practically all tissues and play a role in regeneration and homeostasis. They have the ability to self-renew and activate multipotency when stimulated by biochemical signals. The MSC secretome or MSC-derived extracellular vesicles (exosomes and microvesicles, EVs) have been hypothesized as a more important biological mechanism contributing to their function than their differentiation capacity. EVs play a role in cell-to-cell communication, cell signaling, and changing cell or tissue metabolism at the local or global level. MSC-derived exosomes contain, e.g., cytokines and growth factors, signaling lipids, mRNAs, and regulatory miRNAs.

The contents of MSC exosomes are dynamic, influenced by the MSC tissue of origin, its activity, and its immediate intercellular neighbors. Thus, when MSCs are grown alongside tumor cells or in the in vivo tumor microenvironment, the exosome concentration appears to be altered. MSCs can directly donate mitochondria to recover from cell injury and rescue mitochondrial damage-induced tissue degeneration. This could promote cancer growth and spread by promoting mitochondrial exchange between cancer cells and adjacent stromal cells. A growing body of evidence implies that physical stimulation has a role in MSC development.

We aim to highlight new areas of research related to MSC involvement in niche-specific development, tissue homeostasis, and function, with emphasis on the molecular level. This research will open the way for deciphering the molecular mysteries of MSCs, as well as for novel therapeutic modalities.

Prof. Dr. Marcel Costuleanu
Guest Editor

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Keywords

  • mesenchymal stem cell
  • MSC
  • niche
  • tissue homeostasis
  • exosomes
  • microvesicles
  • cancer
  • mitochondrial exchange
  • MSC secretome

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Published Papers (3 papers)

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18 pages, 83558 KB  
Article
Treatment of Chronic Liver Fibrosis: Adipose and Bone Marrow Mesenchymal Stem Cells
by Murat Shagidulin, Artem Venediktov, Alexei Grigoriev, Mila Ibragimova, Artur Aktemirov, Aglaya Arzhanova, Pavel Fadeev, Valekh Ashyrov, Viktoria Gartseva, Anastasia Kostysheva, Ivan Lychagin, Anna Ponomareva, Lidia Salomatina, Alina Vaniukova, Alla Nikolskaya, Sergei Pershikov, Egor Kuzmin, Ksenia Pokidova, Nikolai Zharov, Natalia Kartashkina, Yulia Basok, Nina Onishchenko, Gennadii Piavchenko and Sergei Gautieradd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2026, 27(12), 5340; https://doi.org/10.3390/ijms27125340 - 13 Jun 2026
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Abstract
Liver fibrosis is a severe but common disease without an easy-to-access option for efficient treatment. Mesenchymal stem cells (MSCs) of different origins have been tested for antifibrotic effects in vitro, in vivo, and in clinical studies over the two last decades, although the [...] Read more.
Liver fibrosis is a severe but common disease without an easy-to-access option for efficient treatment. Mesenchymal stem cells (MSCs) of different origins have been tested for antifibrotic effects in vitro, in vivo, and in clinical studies over the two last decades, although the comparative efficiency of different subtypes remains not fully understood, especially for long-term survival. In this study, we aimed to compare the long-time persistence of favorable effects in male Wistar rats with liver fibrosis treated using MSCs derived from white adipose tissue (AdMSCs) and bone marrow (BMSCs). Liver fibrosis was induced by carbon tetrachloride. We studied the survival rate; oxidative index, assessed via laser Doppler flowmetry; hepatic markers in blood plasma—albumin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase; the ratio of liver to body mass; histological parameters—the number of adipocytes, lymphocytes, siderophages, and Ki67+ cells; and the relative areas of connective tissue proper and reticular fibers. Extra mortality was only typical for fibrotic animals subjected to the sham treatment in the first two weeks. Up to Day 270 of this study, both MSC-treated groups showed barely any differences from animals undergoing the sham treatment in terms of the oxidative index and blood markers, although AdMSC-treated rats presented a more favorable histological pattern than BMSC-treated ones, considering the relative area of reticular fibers and the Ki67 cell count. This study suggests that AdMSC treatments may be more appropriate than BMSC treatments in animal liver fibrosis models, with the results showing better potential for liver tissue regeneration 9 months after treatment. Full article
(This article belongs to the Special Issue Latest Research on Mesenchymal Stem Cells (2nd Edition))
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15 pages, 4594 KB  
Article
Comparative Analysis of Ectodermal Marker Expression in Human Adipose-Derived Stem Cells and Amniotic Epithelial Cells Exposed to Ectoderm-Inducing Conditions
by Bartosz Sikora, Aleksandra Skubis-Sikora, Marcin Ciekalski, Patrycja Wieczorek, Agnieszka Prusek-Kucharek and Piotr Czekaj
Int. J. Mol. Sci. 2026, 27(11), 4976; https://doi.org/10.3390/ijms27114976 - 30 May 2026
Cited by 1 | Viewed by 325
Abstract
Nervous system and corneal disorders are major causes of permanent disability worldwide, largely due to the limited regenerative capacity of ectoderm-derived tissues. Therefore, the development of accessible and ethically acceptable cell-based therapies promoting the repair and regeneration of these tissues is of considerable [...] Read more.
Nervous system and corneal disorders are major causes of permanent disability worldwide, largely due to the limited regenerative capacity of ectoderm-derived tissues. Therefore, the development of accessible and ethically acceptable cell-based therapies promoting the repair and regeneration of these tissues is of considerable translational importance. In this study, we aimed to comparatively evaluate the ectodermal differentiation potential of human adipose-derived stem cells (ADSCs) and human amniotic epithelial cells (hAECs) in vitro, with hAECs serving as a reference cell population with established ectodermal plasticity. Primary ADSCs and hAECs were characterized phenotypically using flow cytometry and functional differentiation assays. Cells were subjected to a directed ectodermal differentiation protocol and assessed via morphological analysis, immunostaining for ectoderm-associated proteins, and RT-qPCR analysis of lineage-specific genes. ADSCs exhibited morphological changes following differentiation, including a more epithelial-like phenotype and an increased nucleus-to-cytoplasm ratio. Immunostaining revealed the induction of nestin and OTX2 expression after differentiation, which was particularly pronounced in ADSCs. Gene expression analysis demonstrated statistically significant upregulation of the ectoderm-related genes EN2, SOX1, and PAX6 exclusively in hAECs. Results suggest that in ADSCs the differentiation process was only partially activated. In conclusion, our findings further support the suitability of hAECs as a reference cell line for studies investigating ectodermal differentiation protocols, while also demonstrating that ADSCs exhibit a limited but detectable capacity for acquiring ectoderm-specific characteristics under defined in vitro culture conditions. Full article
(This article belongs to the Special Issue Latest Research on Mesenchymal Stem Cells (2nd Edition))
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17 pages, 1094 KB  
Article
An HPLC-Based Multi-Analyte Secretome Characterization Panel for Canine Adipose-Derived Mesenchymal/Stromal Stem Cells: Quantification of Adenosine, Kynurenine, IL-10, and TGF-β in Conditioned Media—A Pilot Feasibility Study
by Steven Garner, Emily Laughrun, Susan Mooney, Michael McCord, Seymone Batiste, Melinda Wharton, Rosa Bañuelos and Lori McCord
Int. J. Mol. Sci. 2026, 27(9), 3791; https://doi.org/10.3390/ijms27093791 - 24 Apr 2026
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Abstract
Mesenchymal stromal/stem cells (MSCs) are increasingly explored for immune-mediated diseases, yet standardized analytical readouts that capture coordinated immunomodulatory output across complementary secretory pathways remain limited. Here, we report the feasibility of an HPLC-based multi-analyte secretome characterization panel that quantifies two small-molecule outputs—adenosine and [...] Read more.
Mesenchymal stromal/stem cells (MSCs) are increasingly explored for immune-mediated diseases, yet standardized analytical readouts that capture coordinated immunomodulatory output across complementary secretory pathways remain limited. Here, we report the feasibility of an HPLC-based multi-analyte secretome characterization panel that quantifies two small-molecule outputs—adenosine and kynurenine—alongside two immunomodulatory proteins—interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β)—in conditioned media from canine adipose-derived MSCs (cAD-MSCs). Canine immune-mediated hemolytic anemia (IMHA) was used as a disease context to motivate the selection of these analytes, given the pro-inflammatory cytokine environment characteristic of this condition. Three independent cAD-MSC lines were evaluated under baseline conditions and following cytokine stimulation with recombinant interferon-gamma (IFN-γ; 100 ng/mL) and tumor necrosis factor-alpha (TNF-α; 50 ng/mL), referred to herein as inflammatory priming or licensing. Conditioned media were collected at 72 h for metabolite analysis and 48 h for protein analysis, and quantified by HPLC using external calibration and peak integration. Across all three lines, licensing produced directionally consistent increases: mean adenosine increased 2.3-fold, mean kynurenine increased 3.1-fold, mean IL-10 increased 1.6-fold, and mean TGF-β increased 1.7-fold compared with unlicensed controls. Metabolite measurements for adenosine and kynurenine are reported with full chromatographic selectivity data; IL-10 and TGF-β measurements by reversed-phase HPLC with UV detection are presented as exploratory/semi-quantitative outputs and will require orthogonal confirmation (e.g., immunoassay) in future work. These findings are preliminary, derived from three independent donor lines with no comparator group, and are intended to support feasibility of the analytical framework rather than establish definitive performance specifications. Collectively, the data support the potential of a multi-analyte HPLC-based characterization panel to capture licensing-responsive secretory shifts across mechanistically complementary pathways, providing a foundation for expanded development and validation. Full article
(This article belongs to the Special Issue Latest Research on Mesenchymal Stem Cells (2nd Edition))
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