HucMSC‐Exosome Mediated‐Wnt4 Signaling Is Required for Cutaneous Wound Healing
By Bin Zhang, Mei Wang, Aihua Gong, Xu Zhang, Xiaodan Wu, Yanhua Zhu, Hui Shi, Lijun Wu, Wei Zhu, Hui Qian and 1 more. Stem Cells, 2015
722 citations recorded by the source corpus.
Mesenchymal stem cell‐derived exosomes (MSC‐Ex) play important roles in tissue injury repair, however, the roles of MSC‐Ex in skin damage repair and its mechanisms are largely unknown. Herein, we examined the benefit of human umbilical cord MSC‐derived exosome (hucMSC‐Ex) in cutaneous wound healing using a rat skin burn model. We found that hucMSC‐Ex‐treated wounds exhibited significantly accelerated re‐epithelialization, with increased expression of CK19, PCNA, collagen I (compared to collagen III) in vivo. HucMSC‐Ex promoted proliferation and inhibited apoptosis of skin cells after heat‐stress in vitro. We also discovered that Wnt4 was contained in hucMSC‐Ex, and hucMSC‐Ex‐derived Wnt4 promoted β‐catenin nuclear translocation and activity to enhance proliferation and migration of skin cells, which could be reversed by β‐catenin inhibitor ICG001. In vivo studies confirmed that the activation of Wnt/β‐catenin by hucMSC‐Ex played a key role in wound re‐epithelialization and cell proliferation. Furthermore, knockdown of Wnt4 in hucMSC‐Ex abrogated β‐catenin activation and skin cell proliferation and migration in vitro. The in vivo therapeutic effects were also inhibited when the expression of Wnt4 in hucMSC‐Ex was interfered. In addition, the activation of AKT pathway by hucMSC‐Ex was associated with the reduction of heat stress‐induced apoptosis in rat skin burn model. Collectively, our findings indicate that exosome‐delivered Wnt4 provides new aspects for the therapeutic strategy of MSCs in cutaneous wound healing. Stem Cells 2015;33:2158–2168
Subfields: Molecular Biology, Rehabilitation
View Paper: https://www.semanticscholar.org/paper/823fc79bd0db504d6c3f2f2d2d35482b89c1bae0
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Citations in the corpus
- Exosome Theranostics: Biology and Translational Medicine (2018, background): “Some studies have also described the pathways of transmembrane signal transduction between exosomes and recipient cells [49].”
- Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes (2019, background): “Exosomes derived from human umbilical cord mesenchymal stem cells enhance angiogenesis during the repair of skin after second-degree burn injury [137].”
- Engineering Bioactive Self-Healing Antibacterial Exosomes Hydrogel for Promoting Chronic Diabetic Wound Healing and Complete Skin Regeneration (2019, background): “This observed phenomenon indicated the sustained release of exosomes could exert a potent effect on angiogenesis, which also confirmed the previous research that exosomes can accelerate angiogenesis and promote wound healing [13, 42, 43].”
- Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications (2020, positive): “They not only participate in the process of tissue repair and injury, 24,25 and have certain therapeutic effects on cardiovascular diseases (like myocardial infarction) 26,27 and neurological diseases, 28 but also can alleviate liver injury and be used in the treatment of liver diseases.”
- Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper (2015, background): “In rat models, MSC-EVs significantly improved perfusion in hind limb ischaemia, accelerated reepithelialization following skin burn and enhanced survival of allogeneic skin grafts (111,119,120).”
- MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity. (2018, background): “The activation of AKT and/or ERK pro-survival signalling by exosomes has been reported to be an essential pathway in exosome-mediated tissue repair and regeneration, and have been demonstrated in wound healing [42], bone repair [43] and myocardial regeneration following ischemia injury [44].”