Dataset Information

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

ABSTRACT: The exosomes are derived from mesenchymal stem cells (MSCs) and may be potentially used as an alternative for cell therapy, for treating diabetic wounds, and aid in angiogenesis. This study, aimed to investigate whether exosomes originated from bone marrow-derived MSCs (BMSCs) preconditioned by deferoxamine (DFO-Exos) exhibited superior proangiogenic property in wound repair and to explore the underlying mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were used for assays involving cell proliferation, scratch wound healing, and tube formation. To test the effects in vivo, streptozotocin-induced diabetic rats were established. Two weeks after the procedure, histological analysis was used to measure wound-healing effects, and the neovascularization was evaluated as well. Our findings demonstrated that DFO-Exos activate the PI3K/AKT signaling pathway via miR-126 mediated PTEN downregulation to stimulate angiogenesis in vitro. This contributed to enhanced wound healing and angiogenesis in streptozotocin-induced diabetic rats in vivo. Our results suggest that, in cell-free therapies, exosomes derived from DFO preconditioned stem cells manifest increased proangiogenic ability.

SUBMITTER: Ding J

PROVIDER: S-EPMC6525840 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Ding Jianing J Wang Xin X Chen Bi B Zhang Jieyuan J Zhang Jieyuan J Xu Jianguang J

BioMed research international 20190505

The exosomes are derived from mesenchymal stem cells (MSCs) and may be potentially used as an alternative for cell therapy, for treating diabetic wounds, and aid in angiogenesis. This study, aimed to investigate whether exosomes originated from bone marrow-derived MSCs (BMSCs) preconditioned by deferoxamine (DFO-Exos) exhibited superior proangiogenic property in wound repair and to explore the underlying mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were used for assays in ...[more]

PMID: 31192260

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Project description:Poor wound healing affects millions of people worldwide each year and needs better therapeutic strategies. Synechococcus elongatus PCC 7942 is a naturally occurring photoautotrophic cyanobacterium that can be easily obtained and large-scale expanded. Here, we investigated the therapeutic efficacy of this cyanobacterium in a mouse model of acute burn injury and whether the secretion of extracellular vesicles (EVs), important mediators of cell paracrine activity, is a key mechanism of the cyanobacterium-induced regulation of wound healing. Methods: The effects of Synechococcus elongatus PCC 7942 on burn wound healing in mice under light or dark conditions were evaluated by measuring wound closure rates, histological and immunofluorescence analyses. A series of assays in vivo and in vitro were conducted to assess the impact of the cyanobacterium on angiogenesis. GW4869 was used to interfere with the secretion of EVs by the cyanobacterium and the abilities of the GW4869-pretreated and untreated Synechococcus elongatus PCC 7942 to regulate endothelial angiogenesis were compared. The direct effects of the cyanobacterium-derived EVs (S. elongatus-EVs) on angiogenesis, wound healing and expressions of a class of pro-inflammatory factors that have regulatory roles in wound healing were also examined. Results: Synechococcus elongatus PCC 7942 treatment under light and dark conditions both significantly promoted angiogenesis and burn wound repair in mice. In vitro, the cyanobacterium enhanced angiogenic activities of endothelial cells, but the effects were markedly blocked by GW4869 pretreatment. S. elongatus-EVs were capable of augmenting endothelial angiogenesis in vitro, and stimulating new blood vessel formation and burn wound healing in mice. The expression of interleukin 6 (IL-6), which has an essential role in angiogenesis during skin wound repair, was induced in wound tissues and wound healing-related cells by S. elongatus-EVs and Synechococcus elongatus PCC 7942. Conclusion: Synechococcus elongatus PCC 7942 has the potential as a promising strategy for therapeutic angiogenesis and wound healing primarily by the delivery of functional EVs, not by its photosynthetic activity. The promotion of IL-6 expression may be a mechanism of the cyanobacterium and its EVs-induced pro-angiogenic and -wound healing effects.

Project description:The application of blood plasma for soft tissue wound healing is receiving much more attention recently. Exosomes are critical paracrine mediators that can be obtained from biological fluids including plasma and be able to induce regenerative effects by transferring bioactive molecules such as microRNAs (miRNAs). This study aimed to investigate the effects of exosomes from human umbilical cord blood plasma (UCB-Exos) on wound healing and to elucidate the underlying mechanism. Methods: UCB-Exos were isolated by ultracentrifugation and subcutaneously injected into full-thickness skin wounds in mice. The efficacy of UCB-Exos on wound healing was evaluated by measuring wound closure rates, histological analysis and immunofluorescence examinations. In vitro, quantitative real-time PCR (qRT-PCR) analysis was performed to detect the expression levels of a class of miRNAs that have positive roles in regulating wound healing. The scratch wound assay, transwell assay and cell counting kit-8 analysis were conducted to assess the effects of UCB-Exos on migration and proliferation of human skin fibroblasts and endothelial cells. Tube formation assay was carried out to test the impact of UCB-Exos on angiogenic tube formation ability of endothelial cells. Meanwhile, by using specific RNA inhibitors or siRNAs, the roles of the candidate miRNA and its target genes in UCB-Exos-induced regulation of function of fibroblasts and endothelial cells were assessed. Results: The local transplantation of UCB-Exos into mouse skin wounds resulted in accelerated re-epithelialization, reduced scar widths, and enhanced angiogenesis. In vitro, UCB-Exos could promote the proliferation and migration of fibroblasts, and enhance the angiogenic activities of endothelial cells. Notably, miR-21-3p was found to be highly enriched in UCB-Exos and served as a critical mediator in UCB-Exos -induced regulatory effects through inhibition of phosphatase and tensin homolog (PTEN) and sprouty homolog 1 (SPRY1). Conclusion: Our results suggest that UCB-Exos are important effectors of plasma activity and can be used as a novel promising strategy for soft tissue wound healing.

Dataset Information

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

Publications

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

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