Role of Mesenchymal Stem/Stromal Cells and Their Extracellular Vesicles in the Regenerative Medicine of Musculoskeletal System

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: 30 June 2026 | Viewed by 1406

Special Issue Editors


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Guest Editor
Department of Orthopaedics, Division of Sports Medicine, Diabetes Research Institute, Cell Transplant Center, Miller School of Medicine, University of Miami, 1450NW 10th Ave, Room 3012, Miami, FL 33136, USA
Interests: mesenchymal stem cells/multipotential stromal cells (MSCs); MSC trophic and immunomodulatory actions; MSC functionalization ex vivo; inflammation and fibrosis reversal; synovitis; osteoarthritis; regenerative sports medicine; regenerative orthopaedics
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Guest Editor
Laboratorio di Biotecnologie Applicate all'Ortopedia, IRCCS Ospedale Galeazzi–Sant’Ambrogio, Via Cristina Belgioioso 173, 20157 Milano, Italy
Interests: regenerative medicine; mesenchymal stromal cells; osteoarthritis; extracellular vesicles; miRNA
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Mesenchymal stem/stromal cells (MSC) and their extracellular vesicles (EVs) play a pivotal role in the field of regenerative medicine, particularly in the repair and regeneration of the musculoskeletal system. MSC possess multilineage differentiation potential, enabling them to give rise to bone, cartilage, tendon, and muscle tissues, making them ideal candidates for treating musculoskeletal disorders. Beyond their differentiation capacity, MSC exert profound paracrine effects through the secretion of bioactive molecules and EVs, which include exosomes and microvesicles. These EVs carry proteins, lipids, and nucleic acids that modulate inflammation, enhance angiogenesis, and promote tissue regeneration by influencing resident cells in damaged tissues. Importantly, MSC-derived EVs offer a cell-free therapeutic alternative that reduces the risks associated with cell-based therapies, such as immune rejection or tumorigenicity. As a result, both MSC and their EVs are being extensively studied for applications in osteoarthritis, intervertebral disc degeneration, bone fractures, and tendon injuries, representing a promising frontier in musculoskeletal regenerative medicine.

In this Special Issue, original research articles, communications and reviews covering the entire field of musculoskeletal system regeneration are welcome. Research areas may include (but not limited to) the following:

  • MSC functionalization (e.g., cell phenotype-based purification, cell priming, 3D cell culturing);
  • MSC-derived EVs functionalization (e.g., modulation of bioactive cargo, targeted delivery and therapeutic capacity);
  • Benefits and limitations of MSC versus MSC-derived EVs for musculoskeletal therapeutic applications;
  • MSC and MSC-derived extracellular vesicle effects on immunomodulation and anabolism;

We look forward to receiving your contributions.

Dr. Dimitrios Kouroupis
Dr. Enrico Ragni
Guest Editors

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Keywords

  • mesenchymal stem/stromal cells
  • extracellular vesicles 
  • musculoskeletal regeneration 
  • immunomodulation 
  • anabolism 
  • cell therapy 
  • cell-free therapy 
  • secretome

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Published Papers (1 paper)

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Research

37 pages, 3842 KB  
Article
Tyrosine–Peptide Analog Modulates Extracellular Vesicles miRNAs Cargo from Mesenchymal Stem/Stromal and Cancer Cells to Drive Immunoregeneration and Tumor Suppression
by Michelle B. R. G. Ley, Karina Galoian, Daniel A. Martinez, Arianna Patel, Reanna Thomas, Tressa R. Parker, Lee Friedman, Allie L. Andryski, Francis J. Hornicek, Thomas M. Best and Dimitrios Kouroupis
Biomolecules 2026, 16(2), 243; https://doi.org/10.3390/biom16020243 - 3 Feb 2026
Viewed by 1044
Abstract
Soft tissue sarcoma remains challenging to treat due to its heterogeneity, stemness-associated survival programs, and resistance to conventional therapies. Extracellular vesicles (EVs) mediate tumor–stroma communication, yet how stemness-targeted therapies reshape EVs-associated miRNAs networks remains unclear. This study profiled EVs miRNAs cargo from infrapatellar [...] Read more.
Soft tissue sarcoma remains challenging to treat due to its heterogeneity, stemness-associated survival programs, and resistance to conventional therapies. Extracellular vesicles (EVs) mediate tumor–stroma communication, yet how stemness-targeted therapies reshape EVs-associated miRNAs networks remains unclear. This study profiled EVs miRNAs cargo from infrapatellar fat pad mesenchymal stem/stromal cells (IFP-MSCs) and sarcoma cells (SCs) under basal conditions and following treatment with a synthetic tyrosine peptide analog (TPA). EVs were isolated, characterized, and subjected to miRNAs profiling and pathway enrichment analyses. TPA induced ≥2-fold regulation of 182 miRNAs, including 49 upregulated and 24 downregulated in IFP-MSC-EVs and 86 upregulated and 23 downregulated in SC-EVs. A conserved core of 149 miRNAs (67.1%) was shared across all EVs groups. Abundant species included miR-3960 and miR-21-5p, while TPA reduced tumor-associated miRNAs such as miR-1246 (~10-fold decrease in IFP-MSC-EVs). Pathway enrichment revealed consistent targeting of cancer, MAPK, Wnt, TGF-β, and immune signaling pathways, with modest increases in mapped gene coverage following TPA treatment. In silico analysis identified distinct EVs miRNA–gene interaction profiles, with VEGFA emerging as a recurrent predicted target. These results demonstrate that stemness-targeted modulation quantitatively reprograms EVs miRNA cargo in a cell-type-dependent manner, reshaping vesicle-mediated signaling networks in sarcoma. Full article
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