ArticleStem cell research & therapy2020
Regenerative and protective effects of dMSC-sEVs on high-glucose-induced senescent fibroblasts by suppressing RAGE pathway and activating Smad pathway.
Article in Stem cell research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 4 of them syntheses that pooled it.
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Who cites it
47 citing papers in PubMed, 4 syntheses or guidelines pooled it, 75 citations in OpenAlex.
- Efficacy of MSC-derived small extracellular vesicles in treating type II diabetic cutaneous wounds: a systematic review and meta-analysis of animal models.Frontiers in endocrinology · 2024Pooled it
- Effect of mesenchymal stromal cells-derived extracellular vesicles as a treatment to heal diabetic wounds: A meta-analysis.International wound journal · 2023Pooled it
- MSC-Derived Extracellular Vesicles to Heal Diabetic Wounds: a Systematic Review and Meta-Analysis of Preclinical Animal Studies.Stem cell reviews and reports · 2022Pooled it
- Efficacy and safety of small extracellular vesicle interventions in wound healing and skin regeneration: A systematic review and meta-analysis of animal studies.Theranostics · 2022Pooled it
- Lawsone modulates oxidative stress, apoptosis, and enhances growth factor expression in human dermal fibroblasts under hyperglycemic conditions.Molecular biology reports · 2026Article
- Exosomal MicroRNAs as theranostic tools in type 2 diabetes and its complications: mechanistic insights and clinical implications.Diabetology & metabolic syndrome · 2026Review
- aFGF rescues high glucose-induced senescent fibroblasts and improves diabetic wound healing by regulating SIRT1/STAT3 pathway.Scientific reports · 2026Article
- PLGA/SF/linagliptin wound matrix-induced membrane promotes diabetic wounds healing by inhibiting macrophage pyroptosis.Regenerative biomaterials · 2026Article
- Adipose-Derived Stem Cell Exosomes in Diabetic Wound Repair: Molecular Crosstalk, Bioengineering Strategies, and Translational Challenges.Stem cells international · 2026Review
- Synergistic integration of exosomes and natural compounds in 3D-printed bioscaffolds: Revolutionizing diabetic wound healing through multifunctional therapeutic platforms.Iranian journal of basic medical sciences · 2026Review
- Exosomes from adipose-derived stem cells: A potential therapeutic strategy for diabetic foot ulcers.World journal of diabetes · 2025Review
- Adipose mesenchymal stem cell-derived extracellular vesicles regulate PINK1/parkin-mediated mitophagy to repair high glucose-induced dermal fibroblast senescence and promote wound healing in rats with diabetic foot ulcer.Acta diabetologica · 2025Article
- Fructose-Induced Glycation End Products Promote Skin-Aging Phenotypes and Senescence Marker Expression in Human Dermal Fibroblasts.International journal of molecular sciences · 2025Article
- From bench to bedside: the research status and application opportunity of extracellular vesicles and their engineering strategies in the treatment of skin defects.Journal of nanobiotechnology · 2025Review
- Flavonoids in Lotus Stamen Extract Inhibit High Glucose-Induced Intracellular Glycation in Fibroblasts by Upregulating the Expression of Glyoxalase 1 and Alleviating Oxidative Stress.Antioxidants (Basel, Switzerland) · 2025Article
- Senescent cells as a target for anti-aging interventions: From senolytics to immune therapies.Journal of translational internal medicine · 2025Article
- Exosome Source Matters: A Comprehensive Review from the Perspective of Diverse Cellular Origins.Pharmaceutics · 2025Review
- Angiogenesis during diabetic wound repair: from mechanism to therapy opportunity.Burns & trauma · 2025Review
- Targeting the AGEs-RAGE axis: pathogenic mechanisms and therapeutic interventions in diabetic wound healing.Frontiers in medicine · 2025Review
- The RAGE Pathway in Skin Pathology Development: A Comprehensive Review of Its Role and Therapeutic Potential.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFibroblasts are crucial for supporting normal wound healing. However, the functional state of these cells is impaired in diabetics because of a high-glucose (HG) microenvironment. Small extracellular vesicles (sEVs) have emerged as a promising tool for skin wound treatment. The aim of this study was to investigate the effects of sEVs derived from human decidua-derived mesenchymal stem cells (dMSC-sEVs) on HG-induced human dermal fibroblast (HDF) senescence and diabetic wound healing and explore the underlying mechanism.
methodsWe first created a HDF senescent model induced by HG in vitro. dMSC-conditioned medium (dMSC-CM) and dMSC-sEVs were collected and applied to treat the HG-induced HDFs. We then examined the proliferation, migration, differentiation, and senescence of these fibroblasts. At the same time, the expressions of RAGE, p21 RAS, Smad2/3, and pSmad2/3 were also analyzed. Furthermore, pSmad2/3 inhibitor (SB431542) was used to block the expression of pSmad2/3 to determine whether dMSC-sEVs improved HDF senescence by activating Smad pathway. Finally, we assessed the effect of dMSC-sEVs on diabetic wound healing.
resultsThe HG microenvironment impaired the proliferation, migration, and differentiation abilities of the HDFs and accelerated their senescence. dMSC-CM containing sEVs improved the proliferation and migration abilities of the HG-induced fibroblasts. dMSC-sEVs internalized by HG-induced HDFs not only significantly promoted HDF proliferation, migration, and differentiation, but also improved the senescent state. Furthermore, dMSC-sEVs inhibited the expression of RAGE and stimulated the activation of Smad signaling pathway in these cells. However, SB431542 (pSmad2/3 inhibitor) could partially alleviate the anti-senescent effects of dMSC-sEVs on HG-induced HDFs. Moreover, the local application of dMSC-sEVs accelerated collagen deposition and led to enhanced wound healing in diabetic mice. The detection of PCNA, CXCR4, α-SMA, and p21 showed that dMSC-sEVs could enhance HDF proliferation, migration, and differentiation abilities and improve HDF senescent state in vivo.
conclusiondMSC-sEVs have regenerative and protective effects on HG-induced senescent fibroblasts by suppressing RAGE pathway and activating Smad pathway, thereby accelerating diabetic wound healing. This indicates that dMSC-sEVs may be a promising candidate for diabetic wound treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.