RGDSP-functionalized peptide hydrogel stimulates growth factor secretion via integrin αv/PI3K/AKT axis for improved wound healing by human amniotic mesenchymal stem cells.

IF 4.3 3区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Frontiers in Bioengineering and Biotechnology Pub Date : 2024-10-14 eCollection Date: 2024-01-01 DOI:10.3389/fbioe.2024.1385931
Wei Wei, Lei Huang, Luoying Chen, Huanhuan He, Yanfei Liu, Yuan Feng, Fengqin Lin, Hui Chen, Qing He, Junhong Zhao, Haihong Li
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Abstract

The wound healing process involves communication among growth factors, cytokines, signaling pathways, and cells in the extracellular matrix, with growth factors acting as key regulators. Although stem cells can promote wound healing by secreting diverse growth factors, their therapeutic potential is hindered by poor survival and engraftment. Mimicking the stem cell-matrix interactions can improve stem cell survival, regulate their fate, and even enhance their paracrine effects. This study investigated the use of composite RGDmix hydrogel, which can support the survival and proliferation of human amniotic mesenchymal stem cells (hAMSCs), and effectively increase the expression of various growth factors, thereby promoting wound re-epithelialization, angiogenesis, and epidermal maturation. At last, the specific role of integrin αv and PI3K/AKT signaling pathways in the secretion of growth factors were examined by silencing them in vitro and in vivo. Results suggested that the RGDmix hydrogel improved the secretion of growth factors by hAMSCs through the RGDSP/integrin αv/PI3K/AKT axis, thereby enhancing the therapeutic effect in wound healing.

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RGDSP功能化多肽水凝胶通过整合素αv/PI3K/AKT轴刺激生长因子分泌,改善人羊膜间充质干细胞的伤口愈合。
伤口愈合过程涉及生长因子、细胞因子、信号通路和细胞外基质细胞之间的交流,其中生长因子是关键的调节因子。虽然干细胞可通过分泌多种生长因子促进伤口愈合,但其治疗潜力却因存活率和移植率低而受到阻碍。模拟干细胞与基质的相互作用可提高干细胞的存活率,调节其命运,甚至增强其旁分泌效应。本研究探讨了复合 RGDmix 水凝胶的使用,它能支持人羊膜间充质干细胞(hAMSCs)的存活和增殖,并有效增加各种生长因子的表达,从而促进伤口再上皮化、血管生成和表皮成熟。最后,通过在体外和体内沉默整合素αv和PI3K/AKT信号通路,研究了它们在生长因子分泌中的特殊作用。结果表明,RGDmix水凝胶通过RGDSP/整合素αv/PI3K/AKT轴改善了hAMSCs分泌生长因子,从而提高了伤口愈合的治疗效果。
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来源期刊
Frontiers in Bioengineering and Biotechnology
Frontiers in Bioengineering and Biotechnology Chemical Engineering-Bioengineering
CiteScore
8.30
自引率
5.30%
发文量
2270
审稿时长
12 weeks
期刊介绍: The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs. In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.
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