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微滤泡:用于体外研究的人类毛囊模型。

The microfollicle: a model of the human hair follicle for in vitro studies.

机构信息

TissUse GmbH, Berlin, Germany.

Institute of Biotechnology, Department of Medical Biotechnology, Technische Universität Berlin, Berlin, Germany.

出版信息

In Vitro Cell Dev Biol Anim. 2020 Dec;56(10):847-858. doi: 10.1007/s11626-020-00513-x. Epub 2020 Nov 10.

Abstract

Access to complex in vitro models that recapitulate the unique markers and cell-cell interactions of the hair follicle is rather limited. Creation of scalable, affordable, and relevant in vitro systems which can provide predictive screens of cosmetic ingredients and therapeutic actives for hair health would be highly valued. In this study, we explore the features of the microfollicle, a human hair follicle organoid model based on the spatio-temporally defined co-culture of primary cells. The microfollicle provides a 3D differentiation platform for outer root sheath keratinocytes, dermal papilla fibroblasts, and melanocytes, via epidermal-mesenchymal-neuroectodermal cross-talk. For assay applications, microfollicle cultures were adapted to 96-well plates suitable for medium-throughput testing up to 21 days, and characterized for their spatial and lineage markers. The microfollicles showed hair-specific keratin expression in both early and late stages of cultivation. The gene expression profile of microfollicles was also compared with human clinical biopsy samples in response to the benchmark hair-growth compound, minoxidil. The gene expression changes in microfollicles showed up to 75% overlap with the corresponding gene expression signature observed in the clinical study. Based on our results, the cultivation of the microfollicle appears to be a practical tool for generating testable insights for hair follicle development and offers a complex model for pre-clinical substance testing.

摘要

获取能够重现毛囊独特标志物和细胞间相互作用的复杂体外模型的途径相当有限。创建可扩展、经济实惠且相关的体外系统,能够对化妆品成分和治疗性毛发生物活性物质进行预测性筛选,将具有很高的价值。在这项研究中,我们探索了微毛囊的特征,这是一种基于原代细胞时空限定共培养的人毛囊类器官模型。微毛囊通过表皮-间充质-神经外胚层的串扰,为外根鞘角质形成细胞、真皮乳头成纤维细胞和黑素细胞提供了一个 3D 分化平台。为了进行测定应用,微毛囊培养物适应了 96 孔板,适合进行高达 21 天的中高通量测试,并对其空间和谱系标志物进行了表征。微毛囊在培养的早期和晚期均表现出毛发特异性角蛋白表达。还比较了微毛囊的基因表达谱与人类临床活检样本对基准毛发生长化合物米诺地尔的反应。微毛囊中的基因表达变化与临床研究中观察到的相应基因表达特征之间的重叠高达 75%。基于我们的结果,微毛囊的培养似乎是生成毛囊发育可测试见解的实用工具,并为临床前物质测试提供了复杂的模型。

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