Role of mesenchymal stem cell conditioned medium on wound healing using a developed 3D skin model.

IF 1.5 4区 医学 Q3 DERMATOLOGY
Moyassar Al-Shaibani, Xiao-Nong Wang, Asif Tulah, Rachel E Crossland, Anne M Dickinson, Penny E Lovat
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引用次数: 0

Abstract

Alternative 3-dimensional (3D) skin models that replicate in vivo human skin are required to investigate important events during wound healing, such as collective cell migration, epidermal layer formation, dermal substrate formation, re-epithelialisation and collagen production. In this study, a matched human 3D skin equivalent model (3D-SEM) was developed from human skin cells (fibroblast and keratinocytes), characterised using haematoxylin and eosin, immunofluorescence staining and microRNA profiling. The 3D-SEM was then functionally tested for its use in wound healing studies. Mesenchymal stem cells (MSCs) were isolated and characterised according to the criteria stipulated by the International Society for Cell Therapy. Cytokine and growth factor secretions were analysed by enzyme-linked immunosorbent assay. MSC-conditioned medium (MSC-CM) was then tested for wound healing capacity using the developed 3D-SEM at different timepoints i.e., at one, two and four weeks. The constructed 3D-SEM showed consistent development of skin-like structures composed of dermal layers and epidermal layers, with the ability to express epidermal differentiation markers and full stratification. They also showed prolonged longevity in culture media, retaining full differentiation and stratification within the four weeks. MicroRNA profiling revealed a strong correlation in microRNA expression between the developed 3D-SEM and the original native skin (p<0.001; R=0.64). Additionally, MSC-CM significantly enhanced migration, proliferation and differentiation of epidermal cells in the wounded models compared to control models at the different timepoints. In conclusion, in this study, the developed 3D-SEM mimicked native skin at the cellular and molecular levels, and clearly showed the important stages of skin regeneration during the healing process. MSC secretome contains growth factors that play a pivotal role in the healing process and could be used as a therapeutic option to accelerate skin healing.

利用开发的三维皮肤模型,研究间充质干细胞条件培养基对伤口愈合的作用。
要研究伤口愈合过程中的重要事件,如细胞集体迁移、表皮层形成、真皮基质形成、再上皮化和胶原蛋白生成等,需要复制体内人体皮肤的替代三维(3D)皮肤模型。在这项研究中,利用人体皮肤细胞(成纤维细胞和角质形成细胞)建立了一个匹配的人体三维皮肤等效模型(3D-SEM),并使用血色素和伊红、免疫荧光染色和 microRNA 图谱进行了表征。然后对 3D-SEM 进行了功能测试,以用于伤口愈合研究。间充质干细胞(MSCs)是根据国际细胞治疗学会规定的标准进行分离和鉴定的。细胞因子和生长因子分泌物通过酶联免疫吸附试验进行分析。然后,在不同的时间点,即一周、两周和四周,使用开发的 3D-SEM 测试间充质干细胞调节培养基(MSC-CM)的伤口愈合能力。构建的 3D-SEM 显示出一致的皮肤样结构发育,由真皮层和表皮层组成,能够表达表皮分化标记和完全分层。它们在培养基中的寿命也较长,在四周内保持了完全分化和分层。微RNA图谱分析表明,所培养的三维-SEM与原始原生皮肤的微RNA表达具有很强的相关性(p
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来源期刊
Journal of wound care
Journal of wound care DERMATOLOGY-
CiteScore
2.90
自引率
10.50%
发文量
215
期刊介绍: Journal of Wound Care (JWC) is the definitive wound-care journal and the leading source of up-to-date research and clinical information on everything related to tissue viability. The journal was first launched in 1992 and aimed at catering to the needs of the multidisciplinary team. Published monthly, the journal’s international audience includes nurses, doctors and researchers specialising in wound management and tissue viability, as well as generalists wishing to enhance their practice. In addition to cutting edge and state-of-the-art research and practice articles, JWC also covers topics related to wound-care management, education and novel therapies, as well as JWC cases supplements, a supplement dedicated solely to case reports and case series in wound care. All articles are rigorously peer-reviewed by a panel of international experts, comprised of clinicians, nurses and researchers. Specifically, JWC publishes: High quality evidence on all aspects of wound care, including leg ulcers, pressure ulcers, the diabetic foot, burns, surgical wounds, wound infection and more The latest developments and innovations in wound care through both preclinical and preliminary clinical trials of potential new treatments worldwide In-depth prospective studies of new treatment applications, as well as high-level research evidence on existing treatments Clinical case studies providing information on how to deal with complex wounds Comprehensive literature reviews on current concepts and practice, including cost-effectiveness Updates on the activities of wound care societies around the world.
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