Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Stimulated by Deferoxamine Accelerate Cutaneous Wound Healing by Promoting Angiogenesis

Jianing, Ding; Wang, Xin; Bi, Chen; Zhang, Jieyuan; Xu, Jianguang

doi:10.1155/2019/9742765

Cited by 160 publications

(171 citation statements)

References 27 publications

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“…Therefore, it is of great importance to control inflammation after tendon injury in order to promote high-quality healing. A growing number of studies have shown that mesenchymal stem cell-derived exosomes could inhibit the early inflammatory response in tendon injury and promote tissue healing [23][24][25]. However, the exact mechanisms by which TSC-Exos influence the healing of tendon injury remain unknown.…”

Section: Discussionmentioning

confidence: 99%

Tendon stem cell-derived exosomes regulate inflammation and promote the high-quality healing of injured tendon

et al. 2020

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Background Tendon stem cells (TSCs) have been reported to hold promises for tendon repair and regeneration. However, less is known about the effects of exosomes derived from TSCs. Therefore, we aimed to clarify the healing effects of TSC-derived exosomes (TSC-Exos) on tendon injury. Methods The Achilles tendons of Sprague-Dawley male rats were used for primary culture of TSCs and tenocytes, and exosomes were isolated from TSCs. The proliferation of tenocytes induced by TSC-Exos was analyzed using an EdU assay; cell migration was measured by cell scratch and transwell assays. We used western blot to analyze the role of the PI3K/AKT and MAPK/ERK1/2 signaling pathways. In vivo, Achilles tendon injury models were created in Sprague-Dawley rats. Rats (n = 54) were then randomly assigned to three groups: the TSC-Exos group, the GelMA group, and the control group. We used immunofluorescence to detect changes in the expression of inflammatory and apoptotic markers at 1 week after surgery. Histology and changes in expression of extracellular matrix (ECM)-related indices were assessed by hematoxylin-eosin (H&E) staining and immunohistochemistry at 2 and 8 weeks. The collagen fiber diameter of the healing tendon was analyzed at 8 weeks by transmission electron microscopy (TEM). Results TSC-Exos were taken up by tenocytes, which promoted the proliferation and migration of cells in a dose-dependent manner; this process may depend on the activation of the PI3K/AKT and MAPK/ERK1/2 signaling pathways. At 1 week after surgery, we found that inflammation and apoptosis were significantly suppressed by TSC-Exos. At 2 and 8 weeks, tendons treated with TSC-Exos showed more continuous and regular arrangement in contrast to disorganized tendons in the GelMA and control groups, and TSC-Exos may help regulate ECM balance and inhibited scar formation. Further, at 8 weeks, the TSC-Exos group had a larger diameter of collagen compared to the control group. Conclusions Our data suggest that TSC-Exos could promote high-quality healing of injured tendon, which may be a promising therapeutic approach for tendon injury.

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Section: Discussionmentioning

confidence: 99%

Tendon stem cell-derived exosomes regulate inflammation and promote the high-quality healing of injured tendon

et al. 2020

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“…Different studies have been carried out to better understand the mechanisms activating the angiogenesis during CSU healing, after being treated with EV. That includes the involvement of several miRNA and the activation of the AKT, ERK, and STAT-3 signaling pathways (Shabbir et al, 2015;Ding et al, 2019;Ren et al, 2019). Additionally, it has been demonstrated that the EV can also enhance the angiogenesis, through the portmanteau of "Wingless" and "Int-1" called "wingless-related integration site" (Wnt)/b-catenin (or canonical Wnt) pathway .…”

Section: Angiogenesismentioning

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.

232

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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“…94,[173][174][175] Several studies have reported that BMSC-derived exosomes significantly promote the regeneration and repair of injured tissues, including cartilage and subchondral bone. 174,[176][177][178][179][180][181] The exosomes as well as MVs/ microparticles (MPs) from TGFβ3-pretreated BMSCs significantly increased the expression of anabolic markers and decreased the levels of catabolic marker genes in osteoarthritic chondrocytes. 182 In addition, these BMSC-derived exosomes could prevent osteoarthritic chondrocytes from undergoing apoptosis.…”

Section: Ultrafiltrationmentioning

confidence: 99%

Exosomes: roles and therapeutic potential in osteoarthritis

Ni¹,

et al. 2020

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Exosomes participate in many physiological and pathological processes by regulating cell-cell communication, which are involved in numerous diseases, including osteoarthritis (OA). Exosomes are detectable in the human articular cavity and were observed to change with OA progression. Several joint cells, including chondrocytes, synovial fibroblasts, osteoblasts, and tenocytes, can produce and secrete exosomes that influence the biological effects of targeted cells. In addition, exosomes from stem cells can protect the OA joint from damage by promoting cartilage repair, inhibiting synovitis, and mediating subchondral bone remodeling. This review summarizes the roles and therapeutic potential of exosomes in OA and discusses the perspectives and challenges related to exosome-based treatment for OA patients in the future.

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Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Stimulated by Deferoxamine Accelerate Cutaneous Wound Healing by Promoting Angiogenesis

Cited by 160 publications

References 27 publications

Tendon stem cell-derived exosomes regulate inflammation and promote the high-quality healing of injured tendon

Tendon stem cell-derived exosomes regulate inflammation and promote the high-quality healing of injured tendon

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

Exosomes: roles and therapeutic potential in osteoarthritis

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