Exosomes from acellular Wharton’s jelly of the human umbilical cord promotes skin wound healing

Bakhtyar, Nazihah; Jeschke, Marc G.; Herer, Elaine; Sheikholeslam, Mohammadali; Amini-Nik, Saeid

doi:10.1186/s13287-018-0921-2

Cited by 64 publications

(60 citation statements)

References 52 publications

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“…EVs isolated from vector controls accelerated wound closure ( Fig. 4C, blue squares), consistent with reports showing that EVs accelerate wound closure (36,(59)(60)(61). In contrast, we observed that TBC1D3-regulated EVs failed to accelerate healing (Fig.…”

Section: Adoptive Transfer Of Tbc1d3-evs Delays Wound Closuresupporting

confidence: 91%

TBC1D3 regulates the payload and biological activity of extracellular vesicles that mediate tissue repair

et al. 2019

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Healthy repair of cutaneous injury is a coordinated response of inflammatory cells, secreted factors, and biologically active extracellular vesicles (EVs). Although constitutive release of EVs into biologic fluids is a hallmark of cultured cells and tumors, their payload and biologic activity appears to be tightly regulated. We show that Tre‐2/Bub2/Cdcl6 (TBC1) domain family member 3 (TBC1D3) drives the release of an EV population that causes a decrease in phosphorylation of the transcription factor signal transducer and activator of transcription 3 in naive recipient cells. To explore the biologic activity of EVs in vivo, we used a mouse model of sterile subcutaneous inflammation to determine the payload and biologic activity of EVs released into the microenvironment by committed myeloid lineages and stroma. Expression of TBC1D3 in macrophages altered the payload of their released EVs, including RNA‐binding proteins, molecular motors, and proteins regulating secretory pathways. A wound‐healing model demonstrated that closure was delayed by EVs released under the control of TBC1D3. We show that modulating the secretory repertoire of a cell regulates EV payload and biologic activity that affects outcomes in tissue repair and establishes a strategy for modifying EVs mediating specific biologic responses.—Qin, S., Dorschner, R. A., Masini, I., Lavoie‐Gagne, O., Stahl, P. D., Costantini, T. W., Baird, A., Eliceiri, B. P. TBC1D3 regulates the payload and biological activity of extracellular vesicles that mediate tissue repair. FASEB J. 33, 6129–6139 (2019). http://www.fasebj.org

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Section: Adoptive Transfer Of Tbc1d3-evs Delays Wound Closuresupporting

confidence: 91%

TBC1D3 regulates the payload and biological activity of extracellular vesicles that mediate tissue repair

et al. 2019

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“…This study also described that the effects of the EV were due, at least in part, to their high content of alpha-2-macroglobulin. Nevertheless, they did not identify the mechanisms by which this protein may act in wound healing (Bakhtyar et al, 2018).…”

Section: Fibroblastsmentioning

confidence: 99%

Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing

Casado-Díaz

Quesada‐Gómez

Dorado

2020

Front. Bioeng. Biotechnol.

221

183

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The cells secrete extracellular vesicles (EV) that may have an endosomal origin, or from evaginations of the plasma membrane. The former are usually called exosomes, with sizes ranging from 50 to 100 nm. These EV contain a lipid bilayer associated to membrane proteins. Molecules such as nucleic acids (DNA, mRNA, miRNA, lncRNA, etc.) and proteins may be stored inside. The EV composition depends on the producer cell type and its physiological conditions. Through them, the cells modify their microenvironment and the behavior of neighboring cells. That is accomplished by transferring factors that modulate different metabolic and signaling pathways. Due to their properties, EV can be applied as a diagnostic and therapeutic tool in medicine. The mesenchymal stromal cells (MSC) have immunomodulatory properties and a high regenerative capacity. These features are linked to their paracrine activity and EV secretion. Therefore, research on exosomes produced by MSC has been intensified for use in cell-free regenerative medicine. In this area, the use of EV for the treatment of chronic skin ulcers (CSU) has been proposed. Such sores occur when normal healing does not resolve properly. That is usually due to excessive prolongation of the inflammatory phase. These ulcers are associated with aging and diseases, such as diabetes, so their prevalence is increasing with the one of such latter disease, mainly in developed countries. This has very important socio-economic repercussions. In this review, we show that the application of MSC-derived EV for the treatment of CSU has positive effects, including accelerating healing and decreasing scar formation. This is because the EV have immunosuppressive and immunomodulatory properties. Likewise, they have the ability to activate the angiogenesis, proliferation, migration, and differentiation of the main cell types involved in skin regeneration. They include endothelial cells, fibroblasts, and keratinocytes. Most of the studies carried out so far are preclinical. Therefore, there is a need to advance more in the knowledge about the conditions of production, isolation, and action mechanisms of EV. Interestingly, their potential application in the treatment of CSU opens the door for the design of new highly effective therapeutic strategies.

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“…Indeed, MSC derivatives (Fig. 2) have, in some cases, been shown to be as therapeutically beneficial as living MSCs [30–33], but have the advantage of being able to pass easily through the circulatory system.…”

Section: Live Cells Dead Cells and Derivativesmentioning

confidence: 99%

Mesenchymal stromal cells and their derivatives – putative therapeutics in the management of autoimmune pancreatitis

Goodman

Davies

2020

FEBS Open Bio

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Autoimmune pancreatitis, a derivative of chronic pancreatitis, frequently causes acute episodes with clinical symptoms parallel to those of acute pancreatitis. Corticosteroids are effective in the treatment of 90% of autoimmune pancreatitis cases, but for the remaining 10%, options are limited. Due to their significant immunomodulatory capabilities, mesenchymal stromal cells (MSCs) have been proposed as a novel treatment strategy for various immune and inflammatory pathologies including those with autoimmune origins. Here, we not only highlight the most recent MSC live‐cell experiments to address acute pancreatitis, but also discuss the opportunities afforded by the emergence of the newly identified field of MSC necrobiology. We conclude that the putative employment of MSC derivatives provides a newer and simpler therapeutic approach that could have significant advantages over the use of cells themselves.

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Exosomes from acellular Wharton’s jelly of the human umbilical cord promotes skin wound healing

Cited by 64 publications

References 52 publications

TBC1D3 regulates the payload and biological activity of extracellular vesicles that mediate tissue repair

TBC1D3 regulates the payload and biological activity of extracellular vesicles that mediate tissue repair

Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing

Mesenchymal stromal cells and their derivatives – putative therapeutics in the management of autoimmune pancreatitis

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