Mesenchymal Stem Cell-Derived Exosomes in Tissue Repair and Regeneration

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

Deadline for manuscript submissions: 10 January 2027 | Viewed by 2303

Special Issue Editors


E-Mail Website
Guest Editor
Regenerative Processing Plant, LLC, Palm Harbor, FL, USA
Interests: mesenchymal stem cells; extracellular vesicles; dry eye disease; inflammatory diseases; tissue repair and regeneration
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Regenerative Processing Plant, LLC, Palm Harbor, FL, USA
Interests: mesenchymal stem cells; extracellular vesicles; inflammatory diseases; tissue repair and regeneration

Special Issue Information

Dear Colleagues, 

Mesenchymal stem cells (MSCs) have become a central focus in regenerative medicine due to their multipotent differentiation capacity, immunomodulatory functions, and ability to secrete a range of bioactive factors that facilitate tissue repair. However, mounting evidence suggests that the therapeutic efficacy of MSCs is largely mediated not through direct cell replacement, but via paracrine signalling, notably through their secretome—particularly extracellular vesicles (EVs), of which exosomes are a key component. MSC-derived exosomes (MSC-exosomes) are nano-sized (30–150 nm) vesicles encapsulated by a lipid bilayer that carry a diverse cargo of proteins, lipids, messenger RNAs, and microRNAs, allowing influence over the cellular environment and modulating various physiological processes. The ability of the MSC-exosomes to mirror the therapeutic potential of their parent cells while offering advantages such as lower immunogenicity, easier storage, and reduced risk of ectopic tissue formation or tumorigenesis makes them an attractive cell-free therapeutic alternative for tissue repair and regeneration. 

Recent studies highlight the critical role of MSC-exosomes in promoting tissue repair by regulating immune responses, enhancing angiogenesis, inhibiting apoptosis, and stimulating cellular proliferation and differentiation. Their regenerative potential has been demonstrated in various conditions, including cardiovascular injury, neurodegenerative diseases, wound healing, and musculoskeletal disorders. Despite their promise, key challenges remain in elucidating the precise mechanisms of MSC-exosome-mediated repair, optimizing isolation protocols, and advancing clinical translation. 

Additionally, the mechanisms by which specific exosomal cargos exert their regenerative effects are still being elucidated. Understanding how the origin, culture conditions, and preconditioning of MSCs affect exosome composition is critical for optimizing their therapeutic potential. 

This Special Issue explores the latest advances in MSC-exosome research, focusing on their role in tissue repair and regeneration. We will explore the emerging role of MSC-exosome-based therapies as a next-generation approach in regenerative medicine by examining the bioactive mechanisms and functional impact of MSC-exosomes in addition to researching their biogenesis, molecular composition, and mechanisms of action, along with current advances in their application across various tissues and organ systems, and the therapeutic and regenerative potential of MSC-exosomes in the regulation of immune responses, preventing cell death, and reduced scarring in damaged tissues, offering a safer and potentially more effective alternative to conventional cell-based strategies. 

Dr. Carl Randall Harrell
Dr. Crissy Fellabaum
Guest Editors

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Keywords

  • MSC
  • vesicles
  • exosomes
  • tissue repair and regeneration

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Published Papers (2 papers)

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Research

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13 pages, 1298 KB  
Article
A New Subpopulation of Extracellular Vesicles Harvested from Osteogenically Induced Mesenchymal Stromal Cells of Surgical Site-Released Tissue
by Laura-Marie Joly, Tobias Tertel, Andrea Sowislok, Bernd Giebel and Marcus Jäger
Biomolecules 2026, 16(2), 289; https://doi.org/10.3390/biom16020289 - 12 Feb 2026
Cited by 1 | Viewed by 651
Abstract
Impaired bone healing is a major challenge in orthopedic and trauma surgery, often causing long-term disability and high costs. While autologous bone grafting is the gold standard, it is limited by donor site morbidity, low availability, and surgical risks. As an alternative, surgical [...] Read more.
Impaired bone healing is a major challenge in orthopedic and trauma surgery, often causing long-term disability and high costs. While autologous bone grafting is the gold standard, it is limited by donor site morbidity, low availability, and surgical risks. As an alternative, surgical site-released tissue (SSRT) collected intraoperatively offers a readily available source of regenerative cells and bioactive factors. This study investigates the potential of SSRT-derived mesenchymal stromal cell (MSC)-like cells and their extracellular vesicles (EVs) to support bone healing in a cell-free approach. SSRT samples from 30 patients undergoing elective hip replacement were collected using a surgical vacuum filter. MSC-like cells were isolated and characterized based on International Society for Cellular Therapy (ISCT) criteria. Interestingly, many SSRT-derived MSC-like cells expressed CD34, a marker typically absent in cultured MSCs but linked to tissue-resident stromal cells, suggesting distinct regenerative properties. These cells also showed slow proliferation rates (P1: 8.7 ± 3.2 days; P2: 8.2 ± 5.4 days). EVs were isolated from osteogenically stimulated (EVsMSC/O+) and unstimulated (EVsMSC/O−) MSCs over three weeks. Antibody profiling revealed distinct cargo compositions, with a notable enrichment of CD13+ EVs in the stimulated group. Further in vivo and functional studies are needed to clarify underlying mechanisms and confirm therapeutic efficacy. Full article
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13 pages, 300 KB  
Review
Mesenchymal Stem/Stromal Cells: A Review for Its Use After Allogeneic Hematopoietic Stem Cell Transplantation
by Ali Durdu, Ugur Hatipoglu, Hakan Eminoglu, Turgay Ulas, Mehmet Sinan Dal and Fevzi Altuntas
Biomolecules 2026, 16(1), 147; https://doi.org/10.3390/biom16010147 - 14 Jan 2026
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Abstract
Mesenchymal stem/stromal cells (MSCs) exhibit broad differentiation capability and strong immunoregulatory potential mediated through intercellular communication and the release of diverse paracrine mediators. They represent a promising but still investigational therapeutic approach for managing complications associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). [...] Read more.
Mesenchymal stem/stromal cells (MSCs) exhibit broad differentiation capability and strong immunoregulatory potential mediated through intercellular communication and the release of diverse paracrine mediators. They represent a promising but still investigational therapeutic approach for managing complications associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). This review provides an updated synthesis of MSC biology, their bidirectional interaction with immune cells, and their functional contribution to the hematopoietic niche. It also evaluates current clinical evidence regarding the therapeutic roles of MSCs and MSC-derived extracellular vesicles (EVs) in acute and chronic graft-versus-host disease (aGVHD/cGVHD), as well as in poor graft function. Mechanistic insights encompass macrophage polarization toward an anti-inflammatory phenotype, inhibition of dendritic cell maturation, enhancement of regulatory T-cell expansion, and modulation of cytokine signaling pathways. Within the bone marrow milieu, MSCs contribute to stromal restoration and angiogenic repair. Recent phase II/III trials in steroid-refractory (SR)-aGVHD have demonstrated overall response rates ranging from 48 to 71%. Efficacy appears particularly enhanced in pediatric patients and with early MSC administration. Across studies, MSC therapy shows a favorable safety profile; however, heterogeneity in response and inconsistent survival outcomes remain notable limitations. For poor graft function, limited prospective studies indicate hematopoietic recovery following third-party MSC infusions, and combination approaches such as co-administration with thrombopoietin receptor agonists are under investigation. MSC-derived EVs emulate many immunomodulatory effects of their parental cells with a potentially safer profile, though clinical validation remains in its infancy. MSC-oriented interventions hold substantial biological and therapeutic promise, offering a favorable safety margin; however, clinical translation is hindered by product variability, suboptimal engraftment and persistence, and inconsistent efficacy across studies. Future directions should emphasize standardized manufacturing and potency assays, biomarker-driven patient and timing selection, optimized conditioning and dosing strategies, and the systematic appraisal of EV-based or genetically modified MSC products through controlled trials. Full article
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