使用3D生物打印的人体皮肤等效物识别强效的HSV抗病毒药物
S Tori Ellison1, Ian Hayman2, Kristy Derr1
1Department of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health; Rockville, Maryland 20850, USA.
bioRxiv : the preprint server for biology
|December 23, 2024
概括
一个新的3D生物打印人体皮肤模型改善了单纯疹病毒 (HSV) 药物发现. 该模型比传统方法更好地预测皮肤细胞中的抗病毒功效,有助于开发新的HSV治疗方法.
科学领域:
- 生物技术是生物技术.
- 病毒学 病毒学
- 皮肤病学 皮肤病学
背景情况:
- 简单疹病毒 (HSV) 感染对全球健康构成挑战,目前的治疗方法 (如阿西克洛维尔) 的疗效有限.
- 阿西克洛维尔与亚临床病毒分泌和耐药性作斗争,需要新的治疗策略.
- 使用二维细胞培养物的现有抗病毒查方法缺乏*in vivo*的相关性,并且无法模仿皮肤组织环境.
研究的目的:
- 为更相关的HSV抗病毒查开发和验证3D生物打印的人体皮肤等效试验.
- 用生理学上准确的*ex vivo*模型识别有力的抗病毒化合物.
- 在3D皮肤环境中评估已知的抗HSV药物的疗效.
主要方法:
- 在96井板格式中建立了3D生物打印的人体皮肤等价物.
- 选了738种不同的化合物的图书馆,以检测抗HSV活性.
- 在2D和3D模型中,比较了阿西克洛维尔和其他抗病毒药物在角质细胞与纤维细胞中的功效.
- 将患者衍生细胞纳入3D平台.
主要成果:
- 3D生物打印皮肤测定成功识别了强大的抗病毒药物,验证了其翻译相关性.
- 与纤维细胞相比,阿西克洛维尔在皮细胞中抑制HSV的效力显著降低.
- 针对HSV酶/酶或宿主复制通路的抗病毒药物在细胞类型和模型中表现出一致的强度.
- 该模型的性能通过其识别已知的抗HSV化合物的能力来验证.
结论:
- 3D生物打印的人体皮肤等效试验为HSV药物发现提供了更具生理相关性的平台.
- 阿西克洛维尔在角质细胞中的有效性降低凸显了目前减少病毒传播的治疗方法的局限性.
- 这种3D模型有助于通过患者衍生细胞早期纳入遗传变异性,增强临床前药物测试.
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