scholarly journals Exosomes from adipose-derived mesenchymal stem cells can promote fibroblasts proliferation, migration, and collagen synthesis via activating Wnt/β-catenin signaling pathway during wound healing

2021 ◽  
Author(s):  
Yu An ◽  
Cong Li ◽  
Quanchen Xu ◽  
Yu Sun ◽  
Zhiguo Wang
Keyword(s):  
Wound Healing ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Skin Wound ◽  
Dependent Manner ◽  
Cutaneous Wound Healing ◽  
Skin Wound Healing ◽  
Cutaneous Wound ◽  
Dose Dependent ◽  
Western Blotting Assay

Abstract Background Differentiation, migration, proliferation of skin fibroblasts are identified as the key factors during the cutaneous wound healing. Adipose-derived mesenchymal stem cells (ADMSCs) have been recorded as possible candidates for wound treatment because of their positive effect on the regeneration of many tissues. Exosomes derived from ADMSCs (ADMSC-Exos), an important signal transduction substance secreted by ADMSCs, have a similar role to ADMSCs in wound healing. However, the effects of ADMSC‐Exos on cutaneous wound healing remain to be unclear. In this study, we tried to explore the role and mechaninsm of ADMSC‐Exos during cutaneous wound healing. Methods Human skin fibroblasts (HSF) and ADMSCs were isolated from skin and adipose tissues of healthy person. ADMSC-Exos were purified from human ADMSCs culture medium by differential ultracentrifugation and identified by Electron microscopy, Nanoparticle tracking, and Western blotting assay. Fibroblasts were treated with different concentrations of ADMSC‐Exos. The proliferation and migration abilities of fibroblasts were analyzed by CCK-8 assay and scratch method. The synthesis of collagen type I (Col-I), collagen type III (Col-III), and α-smooth muscle actin (α-SMA) in fibroblasts was assessed by real-time quantitative polymerase chain reaction and Western blotting assay. A tensional wound model on rat back was used to evaluate the effect of ADMSC-Exos on wound healing. The expression levels of Wntb2 and β-catenin were analyzed by Western blotting and immunohistochemical assay. Results ADMSC-Exos were successfully obtained. ADMSC-Exos could significantly promote the migration and proliferation ability of fibroblasts in a dose-dependent manner in vitro. Compared with the treatment without ADMSC-Exos, the expression levels of Col-I and Col-III in fibroblasts treated with ADMSC-Exos were significantly increased, while the expression level of α-SMA is decreased. Besides, the enhanced expression of Wnt2b and β-catenin proteins confirmed the activation of the Wnt/β-catenin signaling pathway. Conclusions ADMSC-Exos can promote fibroblasts proliferation, migration, and collagen synthesis in a dose-dependent manner and may play a positive role in skin wound healing through Wnt/β-catenin signaling pathway. So our study elucidates part of the mechanism of ADMSC-Exos in wound healing, which illustrates the therapeutic potential of ADMSC-Exos as a new therapeutic approach to promote skin wound healing.

scholarly journals Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jin Liu ◽  
Xinyu Qiu ◽  
Yajie Lv ◽  
Chenxi Zheng ◽  
Yan Dong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Mouse Skin ◽  
Skin Wound ◽  
Therapeutic Effects ◽  
Cutaneous Wound Healing ◽  
Apoptotic Bodies ◽  
Skin Wound Healing ◽  
Cutaneous Wound

Abstract Background As the major interface between the body and the external environment, the skin is liable to various injuries. Skin injuries often lead to severe disability, and the exploration of promising therapeutic strategies is of great importance. Exogenous mesenchymal stem cell (MSC)-based therapy is a potential strategy due to the apparent therapeutic effects, while the underlying mechanism is still elusive. Interestingly, we observed the extensive apoptosis of exogenous bone marrow mesenchymal stem cells (BMMSCs) in a short time after transplantation in mouse skin wound healing models. Considering the roles of extracellular vesicles (EVs) in intercellular communication, we hypothesized that the numerous apoptotic bodies (ABs) released during apoptosis may partially contribute to the therapeutic effects. Methods ABs derived from MSCs were extracted, characterized, and applied in mouse skin wound healing models, and the therapeutic effects were evaluated. Then, the target cells of ABs were explored, and the effects of ABs on macrophages were investigated in vitro. Results We found ABs derived from MSCs promoted cutaneous wound healing via triggering the polarization of macrophages towards M2 phenotype. In addition, the functional converted macrophages further enhanced the migration and proliferation abilities of fibroblasts, which together facilitated the wound healing process. Conclusions Collectively, our study demonstrated that transplanted MSCs promoted cutaneous wound healing partially through releasing apoptotic bodies which could convert the macrophages towards an anti-inflammatory phenotype that plays a crucial role in the tissue repair process.

scholarly journals Impact of Ergothioneine, Hercynine, and Histidine on Oxidative Degradation of Hyaluronan and Wound Healing

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 95
Author(s):  
Katarina Valachova ◽  
Karol Svik ◽  
Csaba Biro ◽  
Maurice N. Collins ◽  
Rastislav Jurcik ◽  
...  
Keyword(s):  
Wound Healing ◽  
Oxidative Degradation ◽  
Composite Membranes ◽  
Skin Wound ◽  
Oh Radicals ◽  
Dependent Manner ◽  
Skin Wound Healing ◽  
Radical Degradation ◽  
Dose Dependent

A high-molecular weight hyaluronan is oxidatively degraded by Cu(II) ions and ascorbate—the so called Weissberger biogenic oxidative system—which is one of the most potent generators of reactive oxygen species, namely •OH radicals. Ergothioneine, hercynine, or histidine were loaded into chitosan/hyaluronan composite membranes to examine their effect on skin wound healing in ischemic rabbits. We also explored the ability of ergothioneine, hercynine, or histidine to inhibit hyaluronan degradation. Rotational viscometry showed that ergothioneine decreased the degree of hyaluronan radical degradation in a dose-dependent manner. While histidine was shown to be potent in scavenging •OH radicals, however, hercynine was ineffective. In vivo results showed that the addition of each investigated agent to chitosan/hyaluronan membranes contributed to a more potent treatment of ischemic skin wounds in rabbits compared to untreated animals and animals treated only with chitosan/hyaluronan membranes.

scholarly journals Sodium humate accelerates cutaneous wound healing by activating TGF-β/Smads signaling pathway in rats

2016 ◽  
Vol 6 (2) ◽  
pp. 132-140 ◽  
Author(s):  
Yuanyuan Ji ◽  
Aijun Zhang ◽  
Xiaobin Chen ◽  
Xiaoxia Che ◽  
Kai Zhou ◽  
...  
Keyword(s):  
Wound Healing ◽  
Signaling Pathway ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Sodium Humate

Acemannan accelerates cell proliferation and skin wound healing through AKT/mTOR signaling pathway

2015 ◽  
Vol 79 (2) ◽  
pp. 101-109 ◽  
Author(s):  
Wei Xing ◽  
Wei Guo ◽  
Cun-Hua Zou ◽  
Ting-Ting Fu ◽  
Xiang-Yun Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Signaling Pathway ◽  
Skin Wound ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Skin Wound Healing

Quercetin promotes human epidermal stem cell proliferation through the estrogen receptor/β-catenin/c-Myc/cyclin A2 signaling pathway

2020 ◽  
Vol 52 (10) ◽  
pp. 1102-1110
Author(s):  
Zhaodong Wang ◽  
Guangliang Zhang ◽  
Yingying Le ◽  
Jihui Ju ◽  
Ping Zhang ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Proliferation ◽  
Wound Healing ◽  
Estrogen Receptor ◽  
Signaling Pathway ◽  
Skin Wound ◽  
Skin Tissue ◽  
Skin Wound Healing ◽  
Skin Tissue Engineering ◽  
Cyclin A2

Abstract Skin epidermal stem cells (EpSCs) play an important role in wound healing. Quercetin is a phytoestrogen reported to accelerate skin wound healing, but its effect on EpSCs is unknown. In this study, we investigated the effect of quercetin on human EpSC proliferation and explored the underlying mechanisms. We found that quercetin at 0.1~1 μM significantly promoted EpSC proliferation and increased the number of cells in S phase. The pro-proliferative effect of quercetin on EpSCs was confirmed in cultured human skin tissue. Mechanistic studies showed that quercetin significantly upregulated the expressions of β-catenin, c-Myc, and cyclins A2 and E1. Inhibitor for β-catenin or c-Myc significantly inhibited quercetin-induced EpSC proliferation. The β-catenin inhibitor XAV-939 suppressed quercetin-induced expressions of β-catenin, c-Myc, and cyclins A2 and E1. The c-Myc inhibitor 10058-F4 inhibited the upregulation of c-Myc and cyclin A2 by quercetin. Pretreatment of EpSCs with estrogen receptor (ER) antagonist ICI182780, but not the G protein-coupled ER1 antagonist G15, reversed quercetin-induced cell proliferation and upregulation of β-catenin, c-Myc, and cyclin A2. Collectively, these results indicate that quercetin promotes EpSC proliferation through ER-mediated activation of β-catenin/c-Myc/cyclinA2 signaling pathway and ER-independent upregulation of cyclin E1 and that quercetin may accelerate skin wound healing through promoting EpSC proliferation. As EpSCs are used not only in clinic to treat skin wounds but also as seed cells in skin tissue engineering, quercetin is a useful reagent to expand EpSCs for basic research, skin wound treatment, and skin tissue engineering.

Activin B Promotes BMSC-Mediated Cutaneous Wound Healing by Regulating Cell Migration via the JNK—ERK Signaling Pathway

2014 ◽  
Vol 23 (9) ◽  
pp. 1061-1073 ◽  
Author(s):  
Min Zhang ◽  
Li Sun ◽  
Xueer Wang ◽  
Shixuan Chen ◽  
Yanan Kong ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Signaling Pathway ◽  
Erk Signaling ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound

scholarly journals Exosomes Derived from Dental Pulp Stem Cells Accelerate Cutaneous wound Healing by Enhancing Angiogenesis via Cdc42/p38 MAPK Pathway

2021 ◽  
Author(s):  
Ziyu Zhou ◽  
Jianmao Zheng ◽  
Danle Lin ◽  
Yanan Chen ◽  
Xiaoli Hu
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Dental Pulp ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Protein Levels

Abstract Background: Skin wound healing is a common challenging clinical problem and need advanced treatment strategies. Here, we investigated the therapeutic effects of exosomes derived from dental pulp stem cells (DPSC-Exos) on cutaneous wound healing and the underlying mechanisms. Methods: The effects of DPSC-Exos on cutaneous wound healing in mice were examined by measuring wound closure rates, histological and immunohistochemical analysis. A series of functional assays were performed to evaluate the effects of DPSC-Exos on the angiogenic activities of human umbilical vein endothelial cells (HUVECs) in vitro. TMT-based quantitative proteomic analysis of DPSCs and DPSC-Exos was performed. Gene ontology (GO) and KEGG pathway enrichment analysis were used to evaluate biological functions and pathways for the differentially expressed proteins in DPSC-Exos. Western blot was used to assess the protein levels of Cdc42 and p38 in DPSC-Exos-induced angiogenesis of HUVECs. SB203580, a p38 MAPK signaling pathway inhibitor, was employed to verify the role of p38 MAPK pathway in these processes.Results: Histological and immunohistochemical staining revealed that DPSC-Exos accelerated wound healing by improving neovascularization. DPSC-Exos augmented the migration, proliferation, and capillary formation capacity of HUVECs. Proteomic data demonstrated that proteins contained in DPSC-Exos regulated vasculature development and angiogenesis. Pathway analysis showed that proteins expressed in DPSC-Exos were involved in several pathways including MAPK pathway. Western blotting demonstrated that DPSC-Exos increased the protein levels of Cdc42 and phosphorylation of p38 in HUVECs. SB203580 suppressed the angiogenesis of HUVECs induced by DPSC-Exos.Conclusions: DPSC-Exos could accelerate cutaneous wound healing by enhancing the angiogenic properties of HUVECs via Cdc42/p38 MAPK signaling pathway.

scholarly journals Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Li Hu ◽  
Juan Wang ◽  
Xin Zhou ◽  
Zehuan Xiong ◽  
Jiajia Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Soft Tissue ◽  
Early Stage ◽  
Mouse Skin ◽  
Scar Formation ◽  
Collagen I ◽  
Dependent Manner ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound

Abstract Prolonged healing and scar formation are two major challenges in the treatment of soft tissue trauma. Adipose mesenchymal stem cells (ASCs) play an important role in tissue regeneration, and recent studies have suggested that exosomes secreted by stem cells may contribute to paracrine signaling. In this study, we investigated the roles of ASCs-derived exosomes (ASCs-Exos) in cutaneous wound healing. We found that ASCs-Exos could be taken up and internalized by fibroblasts to stimulate cell migration, proliferation and collagen synthesis in a dose-dependent manner, with increased genes expression of N-cadherin, cyclin-1, PCNA and collagen I, III. In vivo tracing experiments demonstrated that ASCs-Exos can be recruited to soft tissue wound area in a mouse skin incision model and significantly accelerated cutaneous wound healing. Histological analysis showed increased collagen I and III production by systemic administration of exosomes in the early stage of wound healing, while in the late stage, exosomes might inhibit collagen expression to reduce scar formation. Collectively, our findings indicate that ASCs-Exos can facilitate cutaneous wound healing via optimizing the characteristics of fibroblasts. Our results provide a new perspective and therapeutic strategy for the use of ASCs-Exos in soft tissue repair.

Sign in / Sign up

Export Citation Format

Share Document