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Hair follicle (HF) regeneration during wound healing continues to present a significant clinical challenge. Dermal papilla cell-derived exosomes (DPC-Exos) hold immense potential for inducing HF neogenesis. However, the accurate role and underlying mechanisms of DPC-Exos in HF regeneration in wound healing remain to be fully explained. This study, represents the first analysis into the effects of DPC-Exos on fibroblasts during wound healing. Our findings demonstrated that DPC-Exos could stimulate the proliferation and migration of fibroblasts, more importantly, enhance the hair-inducing capacity of fibroblasts. Fibroblasts treated with DPC-Exos were capable of inducing HF neogenesis in nude mice when combined with neonatal mice epidermal cells. In addition, DPC-Exos accelerated wound re-epithelialization and promoted HF regeneration during the healing process. Treatment with DPC-Exos led to increased expression levels of the Wnt pathway transcription factors β-catenin and Lef1 in both fibroblasts and the dermis of skin wounds. Specifically, the application of a Wnt pathway inhibitor reduced the effects of DPC-Exos on fibroblasts and wound healing. Accordingly, these results offer evidence that DPC-Exos promote HF regeneration during wound healing by enhancing the hair-inducing capacity of fibroblasts and activating the Wnt/β-catenin signaling pathway. This suggests that DPC-Exos may represent a promising therapeutic strategy for achieving regenerative wound healing., (© 2024. The Author(s).)

Background: Sepsis is a fatal disease with a high rate of morbidity and mortality, during which acute lung injury is the earliest and most serious complication. Injury of pulmonary microvascular endothelial cells (PMVECs) induced by excessive inflammation plays an important role in sepsis acute lung injury. This study is meant to explore the protective effect and mechanism of ADSCs exosomes on excessive inflammation PMVECs injury., Results: We successfully isolated ADSCs exosomes, the characteristic of which were confirmed. ADSCs exosomes reduced excessive inflammatory response induced ROS accumulation and cell injury in PMVECs. Besides, ADSCs exosomes inhibited excessive inflammatory response induced ferroptosis while upregulated expression of GPX4 in PMVECs. And further GPX4 inhibition experiments revealed that ADSCs exosomes alleviated inflammatory response induced ferroptosis via upregulating GPX4. Meanwhile, ADSCs exosomes could increase the expression and nucleus translocation of Nrf2, while decrease the expression of Keap1. miRNA analysis and further inhibition experiments verified that specific delivery of miR-125b-5p by ADSCs exosomes inhibited Keap1 and alleviated ferroptosis. In CLP induced sepsis model, ADSCs exosomes could relieve the lung tissue injury and reduced the death rate. Besides, ADSCs exosomes alleviated oxidative stress injury and ferroptosis of lung tissue, while remarkably increase expression of Nrf2 and GPX4., Conclusion: Collectively, we illustrated a novel potentially therapeutic mechanism that miR-125b-5p in ADSCs exosomes could alleviate the inflammation induced PMVECs ferroptosis in sepsis induced acute lung injury via regulating Keap1/Nrf2/GPX4 expression, hence improve the acute lung injury in sepsis., Competing Interests: Declaration of compeitng interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Chronic wounds resulting from diabetes are a major health concern in both industrialized and developing countries, representing one of the leading causes of disability and death. This study aimed to investigate the effect of adipose mesenchymal stem cell-derived exosomes (ADSC-exos) on diabetic wounds and the mechanism underlying this effect. The results showed that ADSC-exos could improve oxidative stress and secretion of inflammatory cytokines in diabetic wounds, thereby increasing periwound vascularization and accelerating wound healing. At the cellular level, ADSC-exos reduced reactive oxygen species (ROS) generation in human umbilical vein endothelial cells (HUVECs) and improved mitochondrial function in a high-glucose environment. Moreover, the Western blot analysis showed that the high-glucose environment decreased Sirtuin 3 (SIRT3) expression, while exosome treatment increased SIRT3 expression. The activity of superoxide dismutase 2 (SOD2) was enhanced, and the level of inflammatory cytokines was decreased. Further, SIRT3 interference experiments indicated that the effects of ADSC-exos on oxidative stress and angiogenesis were partly dependent on SIRT3. After SIRT3 was inhibited, ROS production increased, while mitochondrial membrane potential and SOD2 activity decreased. These findings confirmed that ADSC-exos could improve the level of high-glucose-induced oxidative stress, promote angiogenesis, and reduce mitochondrial functional impairment and the inflammatory response by regulating SIRT3/SOD2, thus promoting diabetic wound healing.

Background: Hypertrophic scar (HS) is a fibro-proliferative disorder of dermis after burn or trauma and usually leads to esthetic disfiguration and functionary impairment for patients. Emerging evidences demonstrated ADSC-Exo could alleviate the visceral fibrosis, but little attention had been paid to its role in skin fibrosis. In the study, we would explore the effect of ADSC-Exo on HS and investigated the exact mechanism underlying the properties., Methods: ADSC-Exo were isolated, identified, and internalized by HS-derived fibroblasts (HSFs). The effect of ADSC-Exo on the proliferation and migration of HSFs were detected by flow cytometry and Ki67 immunofluorescence staining, or scratch and trans-wells assays, respectively. RT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry staining were used to evaluate the expression of IL-17RA, Col1, Col3, α-SMA, SIP1, and p-Smad2/p-Smad3 in HSFs stimulated with ADSC-Exo, miR-192-5p mimics, or inhibitors, IL-17RA siRNA and their negative controls. Digital morphology, H&E, Masson's trichrome staining, and immunohistochemistry staining were performed to measure the effect of ADSC-Exo and Lv-IL-17RA shRNA on excisional wound of BALB/c mice., Results: The verified ADSC-Exo effectively inhibited the proliferation and migration of HSFs, decreased the expression of Col1, Col3, α-SMA, IL-17RA, and p-Smad2/p-Smad3 and increased the levels of SIP1 in HSFs. Besides, the mice in ADSC-Exo-treated group demonstrated faster wound healing and less collagen deposition. Furthermore, miR-192-5p was highly expressed in ADSC-Exo and ADSC-Exosomal miR-192-5p ameliorated hypertrophic scar fibrosis. Meanwhile, miR-192-5p targeted the expression of IL-17RA to decrease the pro-fibrotic proteins levels. Moreover, IL-17RA was overexpressed in HS and HSFs, and knockdown IL-17RA alleviated the expression of Col1, Col3, α-SMA, and p-Smad2/p-Smad3 and increased the expression of SIP1 in HSFs. Most importantly, IL-17RA silence also facilitated wound healing, attenuated collagen production, and modulated Smad pathway in HSFs., Conclusions: This study illustrated ADSC-Exo attenuated the deposition of collagen, the trans-differentiation of fibroblasts-to-myofibroblasts, and the formation of hypertrophic scar by in vitro and in vivo experiments. ADSC-Exosomal miR-192-5p targeted IL-17RA to regulate Smad pathway in hypertrophic scar fibrosis. ADSC-Exo could be a promising therapeutic strategy for clinical treatment of hypertrophic scar and the anti-fibrotic properties could be achieved by miR-192-5p/IL-17RA/Smad axis.

ADSCs exosomes, an important means of intercellular communication, can regulate an array of biological processes, including promoting tissue repairs and regeneration, and attenuating inflammation. In this study, we found that ADSCs exosomes could polarize macrophage to an anti-inflammatory phenotype via regulating the expression of Nrf2 and HO-1, and improve inflammatory reaction and injury of multi-organ in sepsis. We revealed that ADSCs exosomes could alleviate LPS induced accumulation of ROS and the expression of inflammatory cytokines IL-1β, TNF-α, and IL-6 in macrophages. Western blot and Flow cytometry results indicated that expression of M1 markers (iNOS and CD86) in LPS stimulated macrophages were significantly declined, while M2 (Arg1 and CD206) were enhanced when pretreated with ADSCs exosomes. Besides, the stress-related molecule HO-1 was upregulated when pretreated with ADSCs exosomes. Further H0-1 interference experiment indicated that anti-inflammatory effect of ADSCs exosomes was dependent on HO-1. Moreover, ADSCs exosomes enhanced expression and nucleus translocation of Nrf2, while downregulated its negative mediator Keap1. In in vivo sepsis models, intravenous injection of ADSCs exosomes relieved inflammatory cytokines storm and organ injury, while promoted expression of HO-1. In conclusion, we proved that ADSCs exosomes alleviated LPS induced inflammation and exerted protective effect in sepsis via regulating Nrf2/HO-1 expression., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Correction to: Stem Cell Research & Therapy (2021) 12:221 https://doi.org/10.1186/s13287-... The original article [[1]] contained an error in author Hongtao Wang's name which has since been corrected. Reference 1 Li Y. Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR-192-5p/IL17RA/Smad axis. [Extracted from the article]

[Display omitted] • This study reveals that endothelial cells injury and ferroptosis is an important reason for unhealing of diabetic wound. • this study for the first time proves that 4OI alleviates high glucose induced endothelial cells ferroptosis by regulating Keap1, Nrf2 and GPX4. • 4OI is for the first time been loaded into H293F exosomes and encapsuled into Alg-DA/GelMA hydrogel. • 4OI-Exo-Gel accelerate diabetic wound healing and alleviate ferroptosis in diabetic wound. The prevalence of diabetic foot ulcer in individuals with diabetes is approximately 15%, and it is frequently accompanied by vascular dysfunction and infection. The management challenges make it the primary cause for amputation; however, the underlying mechanisms remain poorly understood, thereby impeding the advancement of novel wound dressings and medication. Herein, single-cell sequencing analysis revealed that ferroptosis induced by high glucose levels in vascular endothelial cells (VECs) represents a significant molecular pathological feature in diabetic foot ulcer (DFU) tissue. Furthermore, 4-Octyl itaconate (4OI) exhibited a pronounced protective effect against VECs injury induced by high glucose (HG), and its underlying molecular mechanisms involve the mitigation of HG-induced reactive oxygen species (ROS) injury and ferroptosis in VECs through the regulation Keap1/Nrf2/GPX4. For enhanced application, incubation at 37℃ was used to load 4OI into exosomes, which were subsequently encapsulated within an Alg-DA/GelMA-based hydrogel matrix. Remarkably, the utilization of 4OI-Exo-Gel not only expedited wound healing but also significantly improved the overall quality of healing in DFU. In conclusion, these findings not only demonstrate, for the first time, the remarkable ability of 4OI to enhance diabetic wound healing by mitigating VECs ferroptosis induced by HG, but also provide evidence for the potential clinical translation of a 4OI-loaded exosomes hydrogel in diabetic wound therapy. [ABSTRACT FROM AUTHOR]