Ex Vivo Culture Models of Hidradenitis Suppurativa for Defining Molecular Pathogenesis and Treatment Efficacy of Novel Drugs.
Ex Vivo Culture Models of Hidradenitis Suppurativa for Defining Molecular Pathogenesis and Treatment Efficacy of Novel Drugs.
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DOI：
10.1007/s10753-022-01629-w
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发表时间：
2022-06
期刊：
影响因子：
5.1
通讯作者：
中科院分区：
文献类型：
--
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化脓性汗腺炎是一种复杂的炎症性和衰弱性皮肤病，目前尚无有效的治疗方法。部分原因是缺乏适当的人类或动物模型来确定该疾病的病理生物学。在这里，我们描述了空气-液体（A-L）界面，液体浸泡（L-S）和生物反应器（Bio）离体皮肤培养模型的发展。所有三种离体平台均可有效培养皮肤样品达14天。健康皮肤的组织结构和完整性至少保持3天，HS皮肤的组织结构和完整性至少保持14天。直到第3天，在所有三个平台中未观察到早期凋亡细胞百分比的显著差异。然而，在A-L和生物培养中，HS皮肤的晚期凋亡/坏死细胞死亡在第3天增加。这些培养物有效地支持各种细胞群的生长，包括角化细胞和免疫细胞。这些体外培养的HS皮肤炎症基因特征分析显示，在第3天和第14天，它们的表达发生了动态变化。所有三种培养平台都是代表第0天HS皮肤炎症基因状态所必需的，这表明每种培养方法中并非所有基因簇都发生相同的改变。同样，细胞因子/趋化因子分析再次显示，从载体和药物处理的体外HS培养的上清液可以更好地预测药物对HS的疗效。总的来说，这三种培养系统的发展共同为揭示HS进展的病理生物学和筛选各种针对HS的药物提供了有力的工具。
Hidradenitis suppurativa (HS) is a complex inflammatory and debilitating skin disease for which no effective treatment is available currently. This is partly because of the lack of adequate human or animal models for defining the pathobiology of the disease. Here, we describe the development of air-liquid (A-L) interface, liquid-submersion (L-S) and bioreactor (Bio) ex vivo skin culture models. All three ex vivo platforms were effective for culturing skin samples up to 14 days. Tissue architecture and integrity remained intact for at least 3 days for healthy skin and 14 days for HS skin. Up to day-3, no significant differences were observed in % early apoptotic cells among all three platforms. However, the late apoptotic/necrotic cell death was increased in HS skin at day-3 in A-L and Bio culture. These cultures efficiently support the growth of various cells populations, including keratinocytes and immune cells. Profiling inflammatory gene signatures in HS skin from these ex vivo cultures showed dynamic change in their expression at day-3 and day-14. All three culture platforms were necessary to represent the inflammatory gene status of HS skin at day-0, suggesting that not all gene clusters were identically altered in each culture method. Similarly, cytokine/chemokine profiling of the supernatants from vehicle- and drug-treated ex vivo HS cultures again showed better prediction of drug efficacy against HS. Overall, development of these three culture systems collectively provides a powerful tool to uncover the pathobiology of HS progression and screen various drugs against HS.
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影响因子：
10.3
作者：
van der Zee, H. H.;de Ruiter, L.;Prens, E. P.
通讯作者：
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影响因子：
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作者：
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影响因子：
6.5
作者：
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通讯作者：
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影响因子：
8
作者：
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通讯作者：
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