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微球皮肤类器官的生物工程及其在药物筛选中的应用

The Bioengineering of Microspheric Skin Organoids and Their Application in Drug Screening.

作者信息

Xie Jundong, Yang Qingyang, Zhang Yanan, Zheng Ke, Geng Hongya, Wu Yaojiong

机构信息

State Key Laboratory of Chemical Oncogenomics, and Institute of Biopharmaceutical and Health Engineering (iBHE), Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, China.

Key Laboratory of Active Proteins and Peptides Green Biomanufacturing of Guangdong Higher Education Institutes, Tsinghua Shenzhen International Graduate School, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, China.

出版信息

Adv Sci (Weinh). 2025 Jun;12(22):e2416863. doi: 10.1002/advs.202416863. Epub 2025 May 8.

Abstract

It has been a challenge to develop skin models which exhibit the key characteristics of the human skin and facilitate high-throughput drug screening. In this study, a method is developed to construct microspheric skin organoids based on spinning bioreactors. The organoid consists of a core-shell structure to mimic the bilayered skin structure, where the shell is composed of cultured human keratinocytes, resembling the epidermis, and the core, which mimics the dermis, comprises human dermal fibroblasts and collagen. In fabrication of the organoid, the cores are cultured with keratinocytes in spinner flasks under defined conditions to facilitate epidermal growth and differentiation to form mature barrier. To enable efficient drug screening, the organoid is equipped with a luciferase reporter to detect canonical Wnt activation, and Minoxidil is identified to induce epidermal Wnt/beta-catenin pathway signaling. Thus, the study has developed a novel method for efficient preparation of uniform microspheric skin organoids with potential applications for high-throughput drug testing and screening.

摘要

开发出具有人类皮肤关键特征并便于进行高通量药物筛选的皮肤模型一直是一项挑战。在本研究中,开发了一种基于旋转生物反应器构建微球皮肤类器官的方法。该类器官具有核壳结构,以模拟双层皮肤结构,其中外壳由培养的人类角质形成细胞组成,类似于表皮,而模拟真皮的核心包含人类真皮成纤维细胞和胶原蛋白。在类器官的制造过程中,将核心与角质形成细胞在转瓶中在特定条件下培养,以促进表皮生长和分化,形成成熟的屏障。为了实现高效的药物筛选,该类器官配备了荧光素酶报告基因以检测经典Wnt激活,并确定米诺地尔可诱导表皮Wnt/β-连环蛋白通路信号传导。因此,该研究开发了一种高效制备均匀微球皮肤类器官的新方法,具有高通量药物测试和筛选的潜在应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b5d/12165074/bd3243f65517/ADVS-12-2416863-g005.jpg

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