scholarly journals Preliminary Study on Human Adipose Stem Cells Promoting Skin Wound Healing Through Notch1 Signaling Pathway

Author(s):  
Yi Wang ◽  
Qinchao Wu ◽  
Yang Zheng ◽  
Chao Wang ◽  
Xu Ding ◽  
...  

Abstract Background: Mesenchymal stem cells (MSCs) have been documented as possible candidates for wound healing treatment because their use could reinforce the regenerative capacity of many tissues. Human adipose stem cells (hADSCs) have the advantages of easy access, large quantity and easy operation. They can be fully applied in the treatment of skin wounds. In this study, we aim to explore the roles and potential mechanisms of hADSCs in cutaneous wound healing.Methods: hADSCs were obtained from human subcutaneous fat. Adipocytes and osteocytes differentiated from hADSCs were determined by staining with Oil Red O and alkaline phosphatase (ALP), respectively. We assessed the effects of hADSCs and hADSC conditional medium (CM) on wound healing in an injury model of mice. Than, we investigated the biological effects of hADSCs on human keratinocytes HaCAT cells in vitro.Results: The results showed that hADSCs could be successfully differentiated into osteogenic and lipogenic cells. hADSCs and hADSCs-CM significantly promote skin wound healing in vivo. hADSCs significantly promoted HaCAT cells proliferation and migration through activating Notch1 signaling pathway, and activated the AKT signaling pathway by Rps6kb1 kinase in HaCAT cells. In addition, we found that hADSCs-mediated activation of Rps6kb1/AKT signaling was dependent on the Notch1 signaling pathway.Conclusion: We demonstrated that hADSCs can promote skin cell-HaCAT cells proliferation and migration via Notch1 pathway, suggesting that hADSCs may provide an alternative therapeutic approach for the treatment of skin injury.

2021 ◽  
Vol 19 (12) ◽  
pp. 2553-2557
Author(s):  
Keyu Yuan ◽  
Yi Sun ◽  
Yu Ji

Purpose: To determine the effect of miR-485-5p on keratinocyte proliferation and migration.Methods: Human primary keratinocytes (HaCaT cells) were treated with different concentrations of transforming growth factor-β1 (TGF)-β1. miR-485-5p expression levels were determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). MTT (3-[4,5-dimethylthiazol-2- yl]-2,5 diphenyl tetrazolium bromide) and wound healing assays were performed to investigate the regulatory effects of miR-485-5p on cell viability and migration of HaCaT cells. Downstream target gene expression of miR-485-5p was determined using a luciferase activity assay.Results: In HaCaT cells, miR-485-5p was time- and dose-dependently downregulated by TGF-β1 treatment (p < 0.05). Forced expression of miR-485-5p decreased cell viability and migration of HaCaT cells (p < 0.05). Knockdown of miR-485-5p enhanced HaCaT cell viability and migration. Integrin subunit alpha-5 (ITGA5) was predicted and verified to be a downstream target of miR-485-5p in HaCaT cells. Overexpression of ITGA5 attenuated the miR-485-5p-induced decrease of HaCaT cell viability and migration (p < 0.05).Conclusion: MiR-485-5p reduces cell proliferation and migration of keratinocytes through the regulation of ITGA5. This mechanism provides a potential therapeutic strategy for skin wound healing. Keywords: ITGA5, Keratinocyte, Cell migration, MiR-485-5p, Cell proliferation, Wound healing


Author(s):  
Sushmitha Sriramulu ◽  
Antara Banerjee ◽  
Ganesan Jothimani ◽  
Surajit Pathak

AbstractObjectivesWound healing is a complex process with a sequence of restoring and inhibition events such as cell proliferation, differentiation, migration as well as adhesion. Mesenchymal stem cells (MSC) derived conditioned medium (CM) has potent therapeutic functions and promotes cell proliferation, anti-oxidant, immunosuppressive, and anti-apoptotic effects. The main aim of this research is to study the role of human umbilical cord-mesenchymal stem cells (UC-MSCs) derived CM in stimulating the proliferation of human keratinocytes (HaCaT).MethodsFirstly, MSC were isolated from human umbilical cords (UC) and the cells were then cultured in proliferative medium. We prepared and collected the CM after 72 h. Morphological changes were observed after the treatment of HaCaT cells with CM. To validate the findings, proliferation rate, clonal efficiency and also gene expression studies were performed.ResultsIncreased proliferation rate was observed and confirmed with the expression of Proliferating Cell Nuclear Antigen (PCNA) after treatment with HaCaT cells. Cell-cell strap formation was also observed when HaCaT cells were treated with CM for a period of 5–6 days which was confirmed by the increased expression of Collagen Type 1 Alpha 1 chain (Col1A1).ConclusionsOur results from present study depicts that the secretory components in the CM might play a significant role by interacting with keratinocytes to promote proliferation and migration. Thus, the CM stimulates cellular proliferation, epithelialization and migration of skin cells which might be the future promising application in wound healing.


2019 ◽  
Vol 19 (3) ◽  
pp. 574-581 ◽  
Author(s):  
He Qiu ◽  
Shuo Liu ◽  
Kelun Wu ◽  
Rui Zhao ◽  
Lideng Cao ◽  
...  

2017 ◽  
Vol 6 (9) ◽  
pp. 297-307 ◽  
Author(s):  
Yuanyuan Li ◽  
Jamie Zhang ◽  
Jiping Yue ◽  
Xuewen Gou ◽  
Xiaoyang Wu

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Cheng Zhang ◽  
Yu Zhu ◽  
Shengdi Lu ◽  
Wanrun Zhong ◽  
Yanmao Wang ◽  
...  

Diabetic wounds, as a kind of refractory wound, are very difficult to heal. Both endothelial progenitor cell (EPC) transplantation and platelet-rich plasma (PRP) can improve diabetic wound healing to some extent. However, PRP application cannot provide reparative cells, while EPC transplantation cannot replenish the required growth factors for wound healing. Thus, when applied alone, neither of these factors is sufficient for effective wound healing. Furthermore, the proliferation, differentiation, and fate of the transplanted EPCs are not well known. Therefore, in this study, we examined the efficacy of combined PRP application with EPC transplantation in diabetic wound healing. Our results indicated that PRP application improved EPC proliferation and migration. The Notch signaling pathway plays a key role in the regulation of the proliferation and differentiation of stem cells and angiogenesis in wound healing. The application of PRP upregulated the Notch pathway-related gene and protein expression in EPCs. Furthermore, experiments with shNotch1-transfected EPCs indicated that PRP enhanced the function of EPCs by upregulating the Notch1 signaling pathway. In vivo studies further indicated that the combination of PRP and EPC transplantation increased neovascularization, reduced wound size, and improved healing in rat wound models. Thus, PRP application can provide the necessary growth factors for wound healing, while EPC transplantation offers the required cells, indicating that the combination of both is a potent novel approach for treating diabetic wounds.


2015 ◽  
Vol 79 (2) ◽  
pp. 101-109 ◽  
Author(s):  
Wei Xing ◽  
Wei Guo ◽  
Cun-Hua Zou ◽  
Ting-Ting Fu ◽  
Xiang-Yun Li ◽  
...  

2014 ◽  
Vol 3 (4) ◽  
pp. 304-314 ◽  
Author(s):  
Michael Sung-Min Hu ◽  
Robert C. Rennert ◽  
Adrian McArdle ◽  
Michael T. Chung ◽  
Graham G. Walmsley ◽  
...  

2020 ◽  
Vol 52 (10) ◽  
pp. 1102-1110
Author(s):  
Zhaodong Wang ◽  
Guangliang Zhang ◽  
Yingying Le ◽  
Jihui Ju ◽  
Ping Zhang ◽  
...  

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.


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