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Cells
Special Issues
Updates on Mesenchymal Stem Cells-Derived Extracellular Vesicles
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Updates on Mesenchymal Stem Cells-Derived Extracellular Vesicles

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 19449

Special Issue Editor

Dr. Carl Randall Harrell

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

Special Issue Information

Dear Colleagues,

Mesenchymal stem cells (MSC) are adult stem cells with potent regenerative and immunoregulatory properties. MSC in juxtacrine; paracrine manner, through the activity of MSC-sourced growth factors; pro-angiogenic molecules; and immunomodulatory cytokines promote the repair and regeneration of injured and inflamed tissues. MSC-derived exosomes (MSC-Exos) are nano-sized extracellular vesicles that contain MSC-sourced bioactive compounds and possess potent regenerative and immunomodulatory properties, similar to their parental cells. Due to their nano-sized dimension and lipid envelope, MSC-Exos easily bypass all biological barriers and deliver their cargo directly in target cells (injured parenchymal cells and immune cells), regulating their survival, phenotype and function. Accordingly, a large number of experimental and clinical studies have demonstrated the therapeutic efficacy of MSC-Exos in the treatment of inflammatory and degenerative diseases. The therapeutic effects of MSC-Exos could be further optimized by upcoming studies which should delineate the exact molecular mechanisms responsible for their beneficial effects in particular diseases, and which should determine the optimal disease-specific therapeutic dose, treatment schedule and route of administration. This Special Issue aims to include original data papers and reviews that describe the molecular mechanisms responsible for MSC-Exos-based tissue repair and regeneration, as well as papers monitoring the effects of MSC-Exos in preclinical models and clinical studies.

Dr. Carl Randall Harrell
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. 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 stem cell-derived exosomes (MSC-Exo)
  • MSC-Exo-based tissue repair and regeneration
  • MSC-Exo-based immunomodulation
  • MSC-Exo-dependent therapy of inflammatory diseases
  • MSC-Exo-based therapy of degenerative diseases

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Related Special Issue

Published Papers (4 papers)

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Research

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20 pages, 7354 KiB  
Article
Human Placental Mesenchymal Stem Cells and Derived Extracellular Vesicles Ameliorate Lung Injury in Acute Respiratory Distress Syndrome Murine Model
by Paulius Valiukevičius, Justinas Mačiulaitis, Dalia Pangonytė, Vitalija Siratavičiūtė, Katarzyna Kluszczyńska, Ugnė Kuzaitytė, Rūta Insodaitė, Ieva Čiapienė, Ramunė Grigalevičiūtė, Vilma Zigmantaitė, Astra Vitkauskienė and Romaldas Mačiulaitis
Cells 2023, 12(23), 2729; https://doi.org/10.3390/cells12232729 - 29 Nov 2023
Cited by 8 | Viewed by 3627
Abstract
This study investigates the therapeutic potential of human placental mesenchymal stem cells (P-MSCs) and their extracellular vesicles (EVs) in a murine model of acute respiratory distress syndrome (ARDS), a condition with growing relevance due to its association with severe COVID-19. We induced ARDS-like [...] Read more.
This study investigates the therapeutic potential of human placental mesenchymal stem cells (P-MSCs) and their extracellular vesicles (EVs) in a murine model of acute respiratory distress syndrome (ARDS), a condition with growing relevance due to its association with severe COVID-19. We induced ARDS-like lung injury in mice using intranasal LPS instillation and evaluated histological changes, neutrophil accumulation via immunohistochemistry, bronchoalveolar lavage fluid cell count, total protein, and cytokine concentration, as well as lung gene expression changes at three time points: 24, 72, and 168 h. We found that both P-MSCs and EV treatments reduced the histological evidence of lung injury, decreased neutrophil infiltration, and improved alveolar barrier integrity. Analyses of cytokines and gene expression revealed that both treatments accelerated inflammation resolution in lung tissue. Biodistribution studies indicated negligible cell engraftment, suggesting that intraperitoneal P-MSC therapy functions mostly through soluble factors. Overall, both P-MSC and EV therapy ameliorated LPS-induced lung injury. Notably, at the tested dose, EV therapy was more effective than P-MSCs in reducing most aspects of lung injury. Full article
(This article belongs to the Special Issue Updates on Mesenchymal Stem Cells-Derived Extracellular Vesicles)
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16 pages, 5984 KiB  
Communication
An Exosome-Rich Conditioned Medium from Human Amniotic Membrane Stem Cells Facilitates Wound Healing via Increased Reepithelization, Collagen Synthesis, and Angiogenesis
by Chan Ho Noh, Sangryong Park, Hye-Rim Seong, Ah-young Lee, Khan-Erdene Tsolmon, Dongho Geum, Soon-Cheol Hong, Tae Myoung Kim, Ehn-Kyoung Choi and Yun-Bae Kim
Cells 2023, 12(23), 2698; https://doi.org/10.3390/cells12232698 - 24 Nov 2023
Cited by 9 | Viewed by 3186
Abstract
Tissue regeneration is an essential requirement for wound healing and recovery of organs’ function. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth [...] Read more.
Tissue regeneration is an essential requirement for wound healing and recovery of organs’ function. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth factors (GFs) and neurotrophic factors (NFs) effective for tissue regeneration. In this study, an exosome-rich conditioned medium (ERCM) was collected from human amniotic membrane stem cells (AMSCs) by cultivating the cells under a low oxygen tension (2% O2 and 5% CO2). The contents of GFs and NFs including keratinocyte growth factor, epidermal growth factor, fibroblast growth factor 1, transforming growth factor–β, and vascular endothelial growth factor responsible for skin regeneration were much higher (10–30 folds) in the ERCM than in normal conditioned medium (NCM). In was found that CM–DiI-labeled exosomes readily entered keratinocytes and fibroblasts, and that ERCM not only facilitated the proliferation of keratinocytes in normal condition, but also protected against H2O2 cytotoxicity. In cell-migration assay, the scratch wound in keratinocyte culture dish was rapidly closed by treatment with ERCM. Such wound-healing effects of ERCM were confirmed in a rat whole skin-excision model: i.e., the wound closure was significantly accelerated, remaining minimal crusts, by topical application of ERCM solution (4 × 109 exosome particles/100 μL) at 4-day intervals. In the wounded skin, the deposition of collagens was enhanced by treatment with ERCM, which was supported by the increased production of collagen-1 and collagen-3. In addition, enhanced angiogenesis in ERCM-treated wounds was confirmed by increased von Willebrand factor (vWF)-positive endothelial cells. The results indicate that ERCM from AMSCs with high concentrations of GFs and NFs improves wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production, in addition to the regulation of angiogenesis and scar tissue formation. Full article
(This article belongs to the Special Issue Updates on Mesenchymal Stem Cells-Derived Extracellular Vesicles)
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Review

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15 pages, 1752 KiB  
Review
NLRP3 Inflammasome as a Potentially New Therapeutic Target of Mesenchymal Stem Cells and Their Exosomes in the Treatment of Inflammatory Eye Diseases
by Carl Randall Harrell, Valentin Djonov, Ana Antonijevic and Vladislav Volarevic
Cells 2023, 12(18), 2327; https://doi.org/10.3390/cells12182327 - 21 Sep 2023
Cited by 9 | Viewed by 2820
Abstract
Due to their potent immunoregulatory and angio-modulatory properties, mesenchymal stem cells (MSCs) and their exosomes (MSC-Exos) have emerged as potential game-changers in regenerative ophthalmology, particularly for the personalized treatment of inflammatory diseases. MSCs suppress detrimental immune responses in the eyes and alleviate ongoing [...] Read more.
Due to their potent immunoregulatory and angio-modulatory properties, mesenchymal stem cells (MSCs) and their exosomes (MSC-Exos) have emerged as potential game-changers in regenerative ophthalmology, particularly for the personalized treatment of inflammatory diseases. MSCs suppress detrimental immune responses in the eyes and alleviate ongoing inflammation in ocular tissues by modulating the phenotype and function of all immune cells that play pathogenic roles in the development and progression of inflammatory eye diseases. MSC-Exos, due to their nano-sized dimension and lipid envelope, easily bypass all barriers in the eyes and deliver MSC-sourced bioactive compounds directly to target cells. Although MSCs and their exosomes offer a novel approach to treating immune cell-driven eye diseases, further research is needed to optimize their therapeutic efficacy. A significant number of experimental studies is currently focused on the delineation of intracellular targets, which crucially contribute to the immunosuppressive and anti-inflammatory effects of MSCs and MSC-Exos. The activation of NLRP3 inflammasome induces programmed cell death of epithelial cells, induces the generation of inflammatory phenotypes in eye-infiltrated immune cells, and enhances the expression of adhesion molecules on ECs facilitating the recruitment of circulating leukocytes in injured and inflamed eyes. In this review article, we summarize current knowledge about signaling pathways that are responsible for NLRP3 inflammasome-driven intraocular inflammation and we emphasize molecular mechanisms that regulate MSC-based modulation of NLRP3-driven signaling in eye-infiltrated immune cells, providing evidence that NLRP3 inflammasome should be considered a potentially new therapeutic target for MSCs and MSC-Exo-based treatment of inflammatory eye diseases. Full article
(This article belongs to the Special Issue Updates on Mesenchymal Stem Cells-Derived Extracellular Vesicles)
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26 pages, 3123 KiB  
Review
Exosomes: A Promising Strategy for Repair, Regeneration and Treatment of Skin Disorders
by Mario Adrián Tienda-Vázquez, Juan Manuel Hanel, Elsa Margarita Márquez-Arteaga, Ana Paola Salgado-Álvarez, Christian Quintus Scheckhuber, José Rafael Alanis-Gómez, Janette Ivone Espinoza-Silva, Manuel Ramos-Kuri, Fabiola Hernández-Rosas, Elda M. Melchor-Martínez and Roberto Parra-Saldívar
Cells 2023, 12(12), 1625; https://doi.org/10.3390/cells12121625 - 14 Jun 2023
Cited by 28 | Viewed by 9063
Abstract
The skin is the organ that serves as the outermost layer of protection against injury, pathogens, and homeostasis with external factors; in turn, it can be damaged by factors such as burns, trauma, exposure to ultraviolet light (UV), infrared radiation (IR), activating signaling [...] Read more.
The skin is the organ that serves as the outermost layer of protection against injury, pathogens, and homeostasis with external factors; in turn, it can be damaged by factors such as burns, trauma, exposure to ultraviolet light (UV), infrared radiation (IR), activating signaling pathways such as Toll-like receptors (TLR) and Nuclear factor erythroid 2-related factor 2 (NRF2), among others, causing a need to subsequently repair and regenerate the skin. However, pathologies such as diabetes lengthen the inflammatory stage, complicating the healing process and, in some cases, completely inhibiting it, generating susceptibility to infections. Exosomes are nano-sized extracellular vesicles that can be isolated and purified from different sources such as blood, urine, breast milk, saliva, urine, umbilical cord bile cells, and mesenchymal stem cells. They have bioactive compounds that, thanks to their paracrine activity, have proven to be effective as anti-inflammatory agents, inducers of macrophage polarization and accelerators of skin repair and regeneration, reducing the possible complications relating to poor wound repair, and prolonged inflammation. This review provides information on the use of exosomes as a promising therapy against damage from UV light, infrared radiation, burns, and skin disorders. Full article
(This article belongs to the Special Issue Updates on Mesenchymal Stem Cells-Derived Extracellular Vesicles)
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