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The Challenges and Opportunities of Mesenchymal Stromal Cells in Regenerative...
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The Challenges and Opportunities of Mesenchymal Stromal Cells in Regenerative Medicine

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 1 October 2026 | Viewed by 3777

Editor

Dr. Lucie Bacakova

E-Mail Website
Guest Editor
Department of Biomaterials and Tissue Engineering, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic
Interests: vascular smooth muscle cells; phenotypic modulation; vascular disease; stem cell differentiation; vascular tissue engineering; regenerative medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The term "mesenchymal stromal cells" has often been used as a synonym for "mesenchymal stem cells", sharing the common abbreviation “MSCs”. However, mesenchymal stromal cells are a broader group of cells, of which mesenchymal stem cells are a subset. The International Society for Cell and Gene Therapy has characterized mesenchymal stromal cells as a bulk population with remarkable secretory, immunomodulatory, and homing properties, while mesenchymal stem cells have been defined as multipotent adherent cells expressing CD73, CD90, and CD105, lacking the expression of hematopoietic and endothelial markers, and capable of differentiating into specific cell types. In addition, the abbreviation "MSCs" has been used to refer to "medicinal signaling cells", emphasizing their similarity to pericytes and thus their role as sentinel cells of the blood-tissue interface, as well as to "multipotent stem cells", i.e., cells capable of differentiating into multiple but limited cell types, which can be not only mesenchymal but also neural or hematopoietic.

Authors contributing to this Special Issue are invited to further clarify the differences or overlaps between the cell groups for which the abbreviation MSCs has been used in the literature for several decades, using not only conventional best practices but also modern methods of single-cell sequencing, mass cytometry, characterization of extracellular vesicles, and/or microRNA. These new findings will further enhance the benefits and reduce the risks of using mesenchymal stromal cells in regenerative medicine, such as cell therapy and tissue engineering.

Dr. Lucie Bacakova
Guest Editor

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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. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • mesenchymal stromal cells
  • mesenchymal stem cells
  • medicinal signaling cells
  • multipotent stem cells
  • paracrine secretion
  • angiogenesis
  • immunomodulation
  • cell therapy
  • cell-free cell-based therapy
  • stem cell differentiation
  • tissue engineering

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Published Papers (4 papers)

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19 pages, 6132 KB  
Article
Mesenchymal Stromal Cells Improve Islet β-Cell Functional Survival: Analysis of Extracellular Vesicle-Trafficked Proteins and miRNAs
by Tzu-Wen Hong, Rosie Sullivan, Ryea Arora, Adya Lonsane, Zekun Lyu, Sara Caxaria, Tien-Chi Huang, Lydia F. Daniels Gatward, Thomas Burgoyne, Aileen J. F. King, Shanta J. Persaud and Peter M. Jones
Cells 2026, 15(11), 992; https://doi.org/10.3390/cells15110992 - 28 May 2026
Viewed by 520
Abstract
Type 1 diabetes is caused by autoimmune destruction of insulin-secreting β-cells within islets of Langerhans. Transplantation of donor islets can improve glycaemic control, but current clinical islet transplantation protocols are compromised by extensive loss of β-cell functional mass soon after implantation. Co-incubation in [...] Read more.
Type 1 diabetes is caused by autoimmune destruction of insulin-secreting β-cells within islets of Langerhans. Transplantation of donor islets can improve glycaemic control, but current clinical islet transplantation protocols are compromised by extensive loss of β-cell functional mass soon after implantation. Co-incubation in vitro or co-transplantation in vivo of mesenchymal stromal cells (MSCs) with isolated islets improves their functional survival, although the underlying mechanisms remain obscure. Here, we show that MSC-derived extracellular vesicles (MSC-EVs) are alone sufficient to recapitulate many of the beneficial effects of MSCs on islet functional survival, offering the possibility of simple cell-free treatments to improve the outcomes of islet transplantation. We used LC- analysis and small RNA sequencing to analyse the protein and microRNA (miRNA) molecular cargos of MSC-EVs. Proteomic analysis identified >100 proteins from the Uniprot Mouse Database, including β-cell G protein-coupled receptor (GPCR) agonists which we have previously shown to enhance β-cell functional survival. MSC-EVs contained ~300 distinct miRNAs and we identified five highly enriched miRNAs that were significantly upregulated in MSC-EV-treated islets, notably miR-21a-5p. MSC-EV treatment also altered the expression of a distinct set of islet mRNAs known to be involved in islet metabolism and function. These observations may enable the further simplification of the islet pretreatment strategy by focusing on defined GMP-grade biologically active molecules rather than whole heterogeneous EV populations. Full article
(This article belongs to the Special Issue The Challenges and Opportunities of Mesenchymal Stromal Cells in Regenerative Medicine)
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22 pages, 16983 KB  
Article
Shared Extracellular Matrix Remodeling and Proteomic Signature in Dupuytren’s Disease and Relapsed Clubfoot Tissue
by Tomas Novotny, Adam Eckhardt, Jarmila Knitlova, Martina Doubkova, Roman Stachon, Filip Hrdina, Tatyana Kobets and Martin Ostadal
Cells 2026, 15(11), 977; https://doi.org/10.3390/cells15110977 - 26 May 2026
Viewed by 394
Abstract
Although Dupuytren’s disease (DD) and relapsed Clubfoot (RC) are clinically distinct conditions, both exhibit fibrotic tissue remodeling and contracture. This exploratory study investigated whether DD and RC share molecular features associated with fibroproliferative contracture. Pathological tissues from DD nodules and contracted tissues from [...] Read more.
Although Dupuytren’s disease (DD) and relapsed Clubfoot (RC) are clinically distinct conditions, both exhibit fibrotic tissue remodeling and contracture. This exploratory study investigated whether DD and RC share molecular features associated with fibroproliferative contracture. Pathological tissues from DD nodules and contracted tissues from RC together with their respective control tissues (n = 6/group), were analyzed using label-free quantitative proteomics. The analysis identified 12 significantly upregulated proteins shared between both pathological conditions relative to their controls (|log2FC| ≥ 1, p ≤ 0.05). These proteins included structural, signaling and tensile stress ECM proteins. Functional enrichment and network analyses revealed partially overlapping dysregulation of pathways associated with ECM organization and degradation, ECM–receptor interaction, matricellular signaling and mechanobiological processes. In DD samples (n = 10), immunohistochemistry confirmed increased expression of fibrosis-associated proteins (α-SMA, TGF-β1, TGFBI, COL III, COL VI, and COL XII) (at least p < 0.01). Despite these similarities, differences in individual protein abundance and collagen crosslinking were observed between tissues. The findings suggest that DD and RC may share aspects of fibrotic ECM-remodeling despite differences in age, localization, and disease origin. These findings provide initial insights into shared ECM-remodeling processes, although their interpretation should consider the relatively small sample size and biological heterogeneity of the analyzed tissues. Full article
(This article belongs to the Special Issue The Challenges and Opportunities of Mesenchymal Stromal Cells in Regenerative Medicine)
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18 pages, 2079 KB  
Article
The Impact of Surgical Trauma-Activated Platelet-Rich Fibrin on Mesenchymal Stromal Cells In Vitro
by René D. Verboket, Lea Usov, Isabell Bohl, Jonas Neijhoft, Marissa Penna-Martinez, Ingo Marzi and Dirk Henrich
Cells 2026, 15(10), 945; https://doi.org/10.3390/cells15100945 - 21 May 2026
Viewed by 328
Abstract
Introduction: platelet-rich fibrin (PRF) is a second-generation platelet concentrate which is known for promoting cell migration, tissue repair, angiogenesis and bone formation. In contrast, the specific effects of trauma-activated PRF on mesenchymal stromal cells (MSC) are not yet fully understood. The present study [...] Read more.
Introduction: platelet-rich fibrin (PRF) is a second-generation platelet concentrate which is known for promoting cell migration, tissue repair, angiogenesis and bone formation. In contrast, the specific effects of trauma-activated PRF on mesenchymal stromal cells (MSC) are not yet fully understood. The present study investigates systemic effects of surgical trauma-activated PRF on MSCs in vitro, analyzing their metabolic activity, inflammatory responses, and regenerative capacity to optimize advanced treatment concepts for severe fractures and injuries. Material & Methods: PRF membranes (T-PRF from trauma patients, C-PRF from healthy controls) were generated. After co-incubation with MSC cells for 24, 72, and 120 h, further investigations of metabolic activity (MTT assay) and gene expression analyses were performed. Results: for MTT assay, results especially showed a significantly higher metabolic activity of T-PRF after 120 h. ELISA-results measuring cytokine levels (CXCL10, IL-6, VEGF, and IDO) exposed a frequent peak in T-PRF group at 72 h, declining slightly at 120 h. In the gene expression analyses, T-PRF exerted a comparatively stronger stimulating effect on MAPK14 and VEGFA after 24 h, while a decrease in gene expression for MAPK8, MAPK14, and RUNX2 was observed over time. Conclusion: surgical trauma-activated PRF seems to be a powerful inducer of early inflammatory and stress responses in MSCs with preserved angiogenic but limited osteogenic signaling. Therefore, a targeted balance between inflammatory activation and sustainable regeneration, as well as optimized preparation and possible combination with immunomodulatory approaches, appear to be crucial for the therapeutic success of PRF-based strategies. Full article
(This article belongs to the Special Issue The Challenges and Opportunities of Mesenchymal Stromal Cells in Regenerative Medicine)
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22 pages, 2026 KB  
Perspective
Beyond Molecular Markers: The Therapeutic Significance of Mesenchymal Stem Cell Deformability in Regenerative Medicine
by Renata Szydlak
Cells 2025, 14(19), 1516; https://doi.org/10.3390/cells14191516 - 28 Sep 2025
Cited by 1 | Viewed by 2051
Abstract
Mesenchymal stem cells (MSCs) are characterized by their unique therapeutic properties, which include the ability to differentiate, secrete paracrine factors, and migrate toward sites of tissue injury. Although classical molecular markers facilitate phenotypic characterization, they do not always reflect the true functional capacity [...] Read more.
Mesenchymal stem cells (MSCs) are characterized by their unique therapeutic properties, which include the ability to differentiate, secrete paracrine factors, and migrate toward sites of tissue injury. Although classical molecular markers facilitate phenotypic characterization, they do not always reflect the true functional capacity of MSCs. This article introduces deformability, i.e., the capacity of cells to deform under mechanical forces, as a novel, integrative marker of MSC biological quality. It examines the relationship between cellular mechanical deformability and key therapeutic attributes, such as stemness, homing ability, and differentiation status. It overviews current measurement techniques, categorized by resolution, throughput, and clinical applicability. The potential applications of deformability in quality control and cell sorting for therapeutic purposes are also discussed. The article proposes that, in addition to molecular features, deformability may serve as a functional biomarker, potentially enhancing the effectiveness of MSC-based therapies. Full article
(This article belongs to the Special Issue The Challenges and Opportunities of Mesenchymal Stromal Cells in Regenerative Medicine)
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