Adipose mesenchymal stem cell exosomes promote wound healing through accelerated keratinocyte migration and proliferation by activating the AKT/HIF-1α axis

Zhang, Yue; Han, Fei; Gu, Liqun; Ji, Peng; Yang, Xuekang; Liu, Mengdong; TAO, K; Hu, Dahai

doi:10.1007/s10735-020-09887-4

Cited by 48 publications

(37 citation statements)

References 43 publications

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“…Therefore, we could conclude that overexpression of the KLF7/AKT/HIF-axis was correlated with the accelerated progression of NSCLC. Interestingly, adipose mesenchymal stem cell-derived exosomes upregulated the phosphorylation of AKT and the expression of HIFexpediting wound healing [36]. Nevertheless, the regulation of KLF7 on the AKT/HIFnot been investigated in the current study, which awaits further validation.…”

Section: Discussionmentioning

confidence: 80%

microRNA-204 shuttled by mesenchymal stem cell-derived exosomes inhibits the migration and invasion of non-small-cell lung cancer cells via the KLF7/AKT/HIF-1α axis

Liu¹,

Zhang²,

Lin³

et al. 2021

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Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide.Accumulating researches have highlighted the ability of exosome-encapsulated microRNAs (miRNAs or miRs) as potential circulating biomarkers for lung cancer. The current study aimed to evaluate the significance of mesenchymal stem cells (MSCs)-derived exosomal miR-204 in the invasion, migration, and epithelial-mesenchymal transition (EMT) of NSCLC cells. Initially, the expression of miR-204 in human NSCLC tissues and cells was determined by RT-qPCR, which demonstrated that miR-204 was downregulated in NSCLC tissues and cells. Next, Krüppel-like factor 7 (KLF7) was predicted and validated to be a target of miR-204 using dual-luciferase reporter gene assay. NSCLC A549 cells were treated with MSCs-derived exosomes, after which the migration and invasion of A549 cells were detected and expression of EMT-related proteins (E-cadherin, N-cadherin, and Vimentin), KLF7, p-AKT/AKT, and HIFresults of gain-and loss-of-function assays revealed that miR-204 overexpression in MSCs-derived exosomes inhibited KLF7 expression and the AKT/HIF-impaired cell migration, invasion, as well as EMT. In conclusion, the key findings of the current study demonstrate that exosomal miR-204 from MSCs possesses anticarcinogenic properties against NSCLC via the KLF7/AKT/HIF-

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Section: Discussionmentioning

confidence: 80%

microRNA-204 shuttled by mesenchymal stem cell-derived exosomes inhibits the migration and invasion of non-small-cell lung cancer cells via the KLF7/AKT/HIF-1α axis

Liu¹,

Zhang²,

Lin³

et al. 2021

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“…Experimental data show that MSC-EVs promote the activity of such wound edge KCs. Zhang with colleagues found that AdMSC-EVs support HaCaT cell migration and proliferation in vitro and accelerate wound healing in vivo [ 167 ]. They determined that such EVs activate the AKT/HIF-1α pathway, which leads to improved wound healing.…”

Section: Stem Cell-derived Extracellular Vesicles In Skin Wound Healingmentioning

confidence: 99%

Extracellular Vesicles in Skin Wound Healing

et al. 2021

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Each year, millions of individuals suffer from a non-healing wound, abnormal scarring, or injuries accompanied by an infection. For these cases, scientists are searching for new therapeutic interventions, from which one of the most promising is the use of extracellular vesicles (EVs). Naturally, EV-based signaling takes part in all four wound healing phases: hemostasis, inflammation, proliferation, and remodeling. Such an extensive involvement of EVs suggests exploiting their action to modulate the impaired healing phase. Furthermore, next to their natural wound healing capacity, EVs can be engineered for better defined pharmaceutical purposes, such as carrying specific cargo or targeting specific destinations by labelling them with certain surface proteins. This review aims to promote scientific awareness in basic and translational research of EVs by summarizing the current knowledge about their natural role in each stage of skin repair and the most recent findings in application areas, such as wound healing, skin regeneration, and treatment of dermal diseases, including the stem cell-derived, plant-derived, and engineered EVs.

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“…Ma et al 69 established a skin injury model by treating human immortalized keratinocytes line (HaCaT) with hydrogen peroxide and proposed that ADSCs-Exos promoted the migration of damaged keratinocytes to regulate ECM remodeling by activating Wnt/β-catenin signaling pathway. Similarly, by constructing a HaCaT cells model and a mouse wound healing model, Zhang et al 70 found that ADSCs-Exos could accelerate the remodeling of wound healing through accelerated keratinocyte migration and proliferation by activating the AKT/HIF-1α axis.…”

Section: The Role Of Adipose-derived Stem Cells Derived Exosomes In Skin Wound Healingmentioning

confidence: 99%

Research Advances in the Application of Adipose-Derived Stem Cells Derived Exosomes in Cutaneous Wound Healing

Zeng

Guo

2021

Ann Dermatol

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Cutaneous wound healing has always been an intractable medical problem for both clinicians and researchers, with an urgent need for more efficacious methods to achieve optimal outcomes morphologically and functionally. Stem cells, the body's rapid response ‘road repair crew,’ being on standby to combat tissue injuries, are an essential part of regenerative medicine. Currently, the use of adipose-derived stem cells (ADSCs), a kind of mesenchymal stem cells with multipotent differentiation and self-renewal capacity, is surging in the field of cutaneous wound healing. ADSCs may exert influences either by releasing paracrine signalling factors or differentiating into mature adipose cells to provide the ‘building blocks’ for engineered tissue. As an important paracrine substance released from ADSCs, exosomes are a kind of extracellular vesicles and carrying various bioactive molecules mediating adjacent or distant intercellular communication. Previous studies have indicated that ADSCs derived exosomes (ADSCs-Exos) promoted skin wound healing by affecting all stages of wound healing, including regulating inflammatory response, promoting proliferation and migration of fibroblasts or keratinocytes, facilitating angiogenesis, and regulating remodeling of extracellular matrix, which have provided new opportunities for understanding how ADSCs-Exos mediate intercellular communication in pathological processes of the skin and therapeutic strategies for cutaneous wound repair. In this review, we focus on elucidating the role of ADSCs-Exos at various stages of cutaneous wound healing, detailing the latest developments, and presenting some challenges necessary to be addressed in this field, with the expectation of providing a new perspective on how to best utilize this powerful cell-free therapy in the future.

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Adipose mesenchymal stem cell exosomes promote wound healing through accelerated keratinocyte migration and proliferation by activating the AKT/HIF-1α axis

Cited by 48 publications

References 43 publications

microRNA-204 shuttled by mesenchymal stem cell-derived exosomes inhibits the migration and invasion of non-small-cell lung cancer cells via the KLF7/AKT/HIF-1α axis

microRNA-204 shuttled by mesenchymal stem cell-derived exosomes inhibits the migration and invasion of non-small-cell lung cancer cells via the KLF7/AKT/HIF-1α axis

Extracellular Vesicles in Skin Wound Healing

Research Advances in the Application of Adipose-Derived Stem Cells Derived Exosomes in Cutaneous Wound Healing

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