In situ monitoring of mitochondrial redox dynamics during cardiac reprogramming using a poly-l-lysine/Matrigel-coated gold nanostructured composite platform

IF 21.8 2区 材料科学 Q1 MATERIALS SCIENCE, COMPOSITES
Kyeong-Mo Koo, Seung Ju Seo, Chang-Dae Kim, Hyeon Yang, Yoonhee Jin, Tae-Hyung Kim
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Abstract

Cardiac regeneration via the direct reprogramming of fibroblasts into chemically induced cardiomyocyte-like cells (CiCMs) offers a potential therapeutic avenue for heart failure. Nonetheless, the absence of non-invasive techniques for evaluating CiCM maturation and functionality while maintaining therapeutic viability poses a considerable challenge. We present poly-l-lysine, and Matrigel double layer–coated gold nanostructured (PMGN) composite platform coupled with an electrochemical (EC) method that effectively monitors mitochondrial redox dynamics in CiCMs. Based on the metabolic transition from glycolysis to oxidative phosphorylation (OXPHOS), this EC method provides precise measurement of fibroblast-to-CiCM conversion in a completely non-destructive manner. Moreover, the PMGN composite platform facilitates the early detection of functional alterations induced by drugs, such as isoproterenol and carbachol, which conventional cell viability assays fail to detect, and exhibits exceptional sensitivity in identifying drug-induced cardiotoxicity. This in situ method offers real-time feedback and rapid quality control during cell preparation, significantly enhancing the safety and efficacy of stem-cell-based therapies for cardiac regeneration.

利用聚赖氨酸/基质涂层金纳米结构复合平台原位监测心脏重编程过程中线粒体氧化还原动力学
通过将成纤维细胞直接重编程为化学诱导的心肌细胞样细胞(cicm),心脏再生为心力衰竭提供了一种潜在的治疗途径。尽管如此,在保持治疗可行性的同时,缺乏评估CiCM成熟度和功能的非侵入性技术,这构成了相当大的挑战。我们提出了聚赖氨酸和Matrigel双层涂层金纳米结构(PMGN)复合平台,结合电化学(EC)方法,有效监测cicm中的线粒体氧化还原动力学。基于糖酵解到氧化磷酸化(OXPHOS)的代谢转变,这种EC方法以完全无损的方式提供了成纤维细胞到cicm转化的精确测量。此外,PMGN复合平台有助于早期检测药物引起的功能改变,如异丙肾上腺素和碳苯酚,这是传统的细胞活力测定无法检测到的,并且在识别药物诱导的心脏毒性方面表现出异常的敏感性。这种原位方法在细胞制备过程中提供实时反馈和快速质量控制,显著提高了干细胞治疗心脏再生的安全性和有效性。
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来源期刊
CiteScore
26.00
自引率
21.40%
发文量
185
期刊介绍: Advanced Composites and Hybrid Materials is a leading international journal that promotes interdisciplinary collaboration among materials scientists, engineers, chemists, biologists, and physicists working on composites, including nanocomposites. Our aim is to facilitate rapid scientific communication in this field. The journal publishes high-quality research on various aspects of composite materials, including materials design, surface and interface science/engineering, manufacturing, structure control, property design, device fabrication, and other applications. We also welcome simulation and modeling studies that are relevant to composites. Additionally, papers focusing on the relationship between fillers and the matrix are of particular interest. Our scope includes polymer, metal, and ceramic matrices, with a special emphasis on reviews and meta-analyses related to materials selection. We cover a wide range of topics, including transport properties, strategies for controlling interfaces and composition distribution, bottom-up assembly of nanocomposites, highly porous and high-density composites, electronic structure design, materials synergisms, and thermoelectric materials. Advanced Composites and Hybrid Materials follows a rigorous single-blind peer-review process to ensure the quality and integrity of the published work.
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