The role of adipose-derived stem cells-derived extracellular vesicles in the treatment of diabetic foot ulcer: Trends and prospects

Deng, Hongkui; Chen, Yong

doi:10.3389/fendo.2022.902130

Cited by 18 publications

(11 citation statements)

References 137 publications

(139 reference statements)

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“…Increasing evidence shows that exosomes derived from ADSCs exhibit anti-inflammatory properties through inducing the polarization of macrophages to the M2 type through the STAT-3 pathway and reducing inflammation. Exosomes contain microRNSAs, which reinforce the acceleration of wound healing [ 51 ]. Additionally, ADSC exosomes promote scarless wound healing by preventing fibroblasts from differentiating into myofibroblasts and resulting in better cosmesis.…”

Section: Resultsmentioning

confidence: 99%

The Efficacy of Stem Cells in Wound Healing: A Systematic Review

Farabi,

Roster,

Hirani

et al. 2024

IJMS

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Wound healing is an intricate process involving coordinated interactions among inflammatory cells, skin fibroblasts, keratinocytes, and endothelial cells. Successful tissue repair hinges on controlled inflammation, angiogenesis, and remodeling facilitated by the exchange of cytokines and growth factors. Comorbid conditions can disrupt this process, leading to significant morbidity and mortality. Stem cell therapy has emerged as a promising strategy for enhancing wound healing, utilizing cells from diverse sources such as endothelial progenitor cells, bone marrow, adipose tissue, dermal, and inducible pluripotent stem cells. In this systematic review, we comprehensively investigated stem cell therapies in chronic wounds, summarizing the clinical, translational, and primary literature. A systematic search across PubMed, Embase, Web of Science, Google Scholar, and Cochrane Library yielded 22,454 articles, reduced to 44 studies after rigorous screening. Notably, adipose tissue-derived mesenchymal stem cells (AD-MSCs) emerged as an optimal choice due to their abundant supply, easy isolation, ex vivo proliferative capacities, and pro-angiogenic factor secretion. AD-MSCs have shown efficacy in various conditions, including peripheral arterial disease, diabetic wounds, hypertensive ulcers, bullous diabeticorum, venous ulcers, and post-Mohs micrographic surgery wounds. Delivery methods varied, encompassing topical application, scaffold incorporation, combination with plasma-rich proteins, and atelocollagen administration. Integration with local wound care practices resulted in reduced pain, shorter healing times, and improved cosmesis. Stem cell transplantation represents a potential therapeutic avenue, as transplanted stem cells not only differentiate into diverse skin cell types but also release essential cytokines and growth factors, fostering increased angiogenesis. This approach holds promise for intractable wounds, particularly chronic lower-leg wounds, and as a post-Mohs micrographic surgery intervention for healing defects through secondary intention. The potential reduction in healthcare costs and enhancement of patient quality of life further underscore the attractiveness of stem cell applications in wound care. This systematic review explores the clinical utilization of stem cells and stem cell products, providing valuable insights into their role as ancillary methods in treating chronic wounds.

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Section: Resultsmentioning

confidence: 99%

The Efficacy of Stem Cells in Wound Healing: A Systematic Review

Farabi,

Roster,

Hirani

et al. 2024

IJMS

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“…DFU wound healing is influenced by multiple factors, and its mechanisms mainly involve hyperglycemic-induced angiogenesis disorders, abnormal inflammatory response, and changes in the migration and proliferation of fibroblasts and keratin-forming cells. The pathological process of DFU is extremely complex and difficult to therapy [ 19 ]. Conventional treatments, such as glycemic control and interventional surgery, have certain limitations [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Circ_072697 knockdown promotes advanced glycation end products-induced cell proliferation and migration in HaCaT cells via miR-3150a-3p/KDM2A axis

Tian,

Tang,

Huang

et al. 2023

BMC Endocr Disord

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Objective Diabetes foot ulcer (DFU) is a serious complication of diabetes, which can lead to significant mortality and amputation rate. Our previous study found circ_072697 was highly expressed in DFU tissues, but the regulatory mechanism of circ_072697 in DFU remains unclear. Methods The relative expressions of circ_072697, miR-3150a-3p, and KDM2A in DFU patients or advanced glycation end products (AGEs)-treated HaCaT cells (used as DFU cell model) were determined by using qRT-PCR. Cell proliferation and migration abilities were determined by using CCK-8 and Transwell assays. The interaction between miR-3150a-3p with circ_072697 or KDM2A were verified by RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. Furthermore, the protein expression of genes involved in MAPK signaling pathway was detected by western blot. Results The expression of circ_072697 was significantly upregulated in DFU tissues, while the expression of miR-3150a-3p was downregulated. Circ_072697 knockdown promoted the proliferation and migration of AGEs-treated HaCaT cells. miR-3150a-3p was confirmed as a target of circ_072697 and its inhibitor reversed the promotion effects of circ_072697 knockdown on biological behavior of cells. In addition, KDM2A was considered as a target of miR-3150a-3p and it was highly expressed in DFU samples. Importantly, circ_072697 could regulate KDM2A expression through sponging miR-3150a-3p, and this axis had effect on the MAPK signaling pathway. Conclusions Overall, circ_072697 regulated the biological behaviors of keratinocytes in DFU via miR-3150a-3p/KDM2A axis and MAPK signaling pathway, revealing a new insight into the pathogenesis and potential therapeutic targets of DFU.

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“…Adipose tissue is rich in stem cells, termed adipose tissue-derived stem cells (ADSCs), which have been reported to have great potential in wound repair and tissue regeneration. Phages polarize to the M2 phenotype to reduce the ability of macrophages to stimulate an inflammatory response, thereby reducing inflammatory responses in wounds [ 82 ]. In a skin injury model mimicking foot ulcers, mesenchymal stem cell (MSC) administration accelerated wound closure by modulating macrophage infiltration and restoring IL-1β and TNF-α mRNA to normal levels [ 83 ].…”

Section: Reviewmentioning

confidence: 99%

Macrophage polarization in diabetic wound healing

et al. 2022

Burns &Amp; Trauma

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Impaired wound healing is one of the severe complications of diabetes. Macrophages have been shown to play a vital role in wound healing. In different wound environments, macrophages are classified into two phenotypes: classically activated macrophages and alternatively activated macrophages. Dysregulation of macrophage phenotypes leads to severely impaired wound healing in diabetes. Particularly, uncontrolled inflammation and abnormal macrophage phenotype are important reasons hindering the closure of diabetic wounds. This article reviews the functions of macrophages at various stages of wound healing, the relationship between macrophage phenotypic dysregulation and diabetic wound healing and the mechanism of macrophage polarization in diabetic wound healing. New therapeutic drugs targeting phagocyte polarization to promote the healing of diabetic wounds might provide a new strategy for treating chronic diabetic wound healing.

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The role of adipose-derived stem cells-derived extracellular vesicles in the treatment of diabetic foot ulcer: Trends and prospects

Cited by 18 publications

References 137 publications

The Efficacy of Stem Cells in Wound Healing: A Systematic Review

The Efficacy of Stem Cells in Wound Healing: A Systematic Review

Circ_072697 knockdown promotes advanced glycation end products-induced cell proliferation and migration in HaCaT cells via miR-3150a-3p/KDM2A axis

Macrophage polarization in diabetic wound healing

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