Cell-free therapy based on adipose tissue stem cell-derived exosomes promotes wound healing via the PI3K/Akt signaling pathway

Zhang, Wei; Bai, Xiaozhi; Zhao, Bin; Li, Yan; Zhang, Yijie; Li, Zhenzhen; Wang, Xujie; Luo, Liang; Han, Fangfang; Zhang, Julei; Han, Shichao; Cai, Wenju; Su, Linlin; Tao, Ke; Shi, Jihong; Hu, Dahai

doi:10.1016/j.yexcr.2018.06.035

Cited by 281 publications

(241 citation statements)

References 36 publications

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“…Exosomes are factors/molecules secreted by cells into the extracellular space, which play a role in intercellular communication. They can be extracted from cell culture media by various methods, including centrifugation, filtration, and ion-exchange chromatography [10]. The size of exosomes can be identified by TEM and NTA, and proteins such as CD63, CD81, TSG101, and HSP70, which are usually rich in exosomes, can be identified by western blot [15].…”

Section: Discussionmentioning

confidence: 99%

“…Exo were also shown to induce the proliferation and migration of vascular endothelial cells, promote angiogenesis, and reduce apoptosis of endothelial cells, indicating important roles in injury repair and vascularization [10,39]. In the current study, we therefore applied ADSC-Exo to artificial dermal prefabricated flaps to overcome the issue of insufficient vascularization.…”

Section: Stem Cells Internationalmentioning

confidence: 98%

“…However, despite the many advantages of ADSCs, technical problems and the risk of tumor formation currently limit their clinical application [9]. Exosomes are membranous vesicles about 30-150 nm in diameter that are released from the intracellular matrix into the extracellular matrix [10]. They can carry a variety of biological macromolecules, including proteins, lipids, and nucleic acids, and participate in various physiological processes, such as the immune response, antigen presentation, and protein and RNA transport [11].…”

Section: Introductionmentioning

confidence: 99%

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Comparison of Proangiogenic Effects of Adipose-Derived Stem Cells and Foreskin Fibroblast Exosomes on Artificial Dermis Prefabricated Flaps

Xiong

Liu

et al. 2020

Stem Cells International

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Large prefabricated flaps often suffer from necrosis or poor healing due to a lack of new blood vessels and related factors that promote angiogenesis. The innovative use of adipose-derived stem cell exosomes (ADSC-Exo) resolves the problem of vascularization of prefabricated flaps. We analyzed the differential microRNA (miRNA) expression in ADSC-Exo using nextgeneration sequencing (NGS) technology to explore their potential mechanisms in promoting vascularization. We observed that ADSC-Exo could significantly promote the vascularization of artificial dermis prefabricated flaps compared with human foreskin fibroblast exosomes. NGS indicated that there were some differentially expressed miRNAs in both exosomes. Bioinformatics analysis suggested that significantly upregulated hsa-miR-760 and significantly downregulated hsa-miR-423-3p in ADSC-Exo could regulate the expression of the ITGA5 and HDAC5 genes, respectively, to promote the vascularization of skin flaps. In summary, ADSC-Exo can promote skin-flap vascularization, and thereby resolve the problem of insufficient neovascularization of artificial dermis prefabricated flaps, thus expanding the application of prefabricated skin-flap transplantation.

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Section: Discussionmentioning

confidence: 99%

Section: Stem Cells Internationalmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Comparison of Proangiogenic Effects of Adipose-Derived Stem Cells and Foreskin Fibroblast Exosomes on Artificial Dermis Prefabricated Flaps

Xiong

Liu

et al. 2020

Stem Cells International

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“…The MSC-derived EV increased the skin re-epithelialization in full-thickness cutaneous wounds in animal models (Robson et al, 2001;Zhang et al, 2015aZhang et al, , 2018Li et al, 2017;Tao et al, 2017;Ren et al, 2019;Wang et al, 2019b). However, there are few works analyzing the specific effects of such EV in keratinocytes.…”

Section: Keratinocytesmentioning

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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“…Similarly, the migration ability of both cell types was also enhanced by administration of ASC-EVs at the same concentration as analyzed through the scratch wound healing assay at 12 and 24 h. Exposure of both cell types to ASC-EVs was also associated with higher levels of phosphorylated Akt and increased activity of the Akt pathway, one of the major biochemical pathways regulating the migration of epithelial cells [77]. More recently, Zhang et al [78] also showed evidence of the involvement of phosphoinositide 3-kinase (PI3K)/Akt signaling in the promoting effect of ASC-Exos of wound healing. Exos were isolated from ASC-CM as follows.…”

Section: In Vitro Studiesmentioning

confidence: 87%

Secretome of Adipose Tissue-Derived Stem Cells (ASCs) as a Novel Trend in Chronic Non-Healing Wounds: An Overview of Experimental In Vitro and In Vivo Studies and Methodological Variables

Lombardi

Palumbo

Augello

et al. 2019

IJMS

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Wound healing is a complex process with a linear development that involves many actors in a multistep timeline commonly divided into four stages: Hemostasis, inflammation, proliferation, and remodeling. Chronic non-healing wounds fail to progress beyond the inflammatory phase, thus precluding the next steps and, ultimately, wound repair. Many intrinsic or extrinsic factors may contribute to such an occurrence, including patient health conditions, age-related diseases, metabolic deficiencies, advanced age, mechanical pressure, and infections. Great interest is being focused on the adipose tissue-derived stem cell’s (ASC) paracrine activity for its potential therapeutic impact on chronic non-healing wounds. In this review, we summarize the results of in vitro and in vivo experimental studies on the pro-wound healing effects of ASC-secretome and/or extracellular vesicles (EVs). To define an overall picture of the available literature data, experimental conditions and applied methodologies are described as well as the in vitro and in vivo models chosen in the reported studies. Even if a comparative analysis of the results obtained by the different groups is challenging due to the large variability of experimental conditions, the available findings are undoubtedly encouraging and fully support the use of cell-free therapies for the treatment of chronic non-healing wounds.

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Cell-free therapy based on adipose tissue stem cell-derived exosomes promotes wound healing via the PI3K/Akt signaling pathway

Cited by 281 publications

References 36 publications

Comparison of Proangiogenic Effects of Adipose-Derived Stem Cells and Foreskin Fibroblast Exosomes on Artificial Dermis Prefabricated Flaps

Comparison of Proangiogenic Effects of Adipose-Derived Stem Cells and Foreskin Fibroblast Exosomes on Artificial Dermis Prefabricated Flaps

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

Secretome of Adipose Tissue-Derived Stem Cells (ASCs) as a Novel Trend in Chronic Non-Healing Wounds: An Overview of Experimental In Vitro and In Vivo Studies and Methodological Variables

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