美国北卡罗来纳大学教堂山分校J. Victor Garcia和Angela Wahl等研究人员，合作开发了可广泛用于人类病原体体内测试的精密小鼠模型。该项研究成果2019年8月26日在线发表于《自然—生物技术》。
研究人员发现将包含多达40种细胞类型（包括非造血细胞）的人肺组织植入免疫缺陷小鼠（只植入肺的小鼠）中会导致高度血管化肺植入物的发育。研究人员证明新出现的和临床相关的人类病原体，如中东呼吸综合症冠状病毒、寨卡病毒、呼吸道合胞病毒和巨细胞病毒在这些肺植入物中发生体内复制。当整合进骨髓/肝脏/胸腺人源化小鼠中时，肺植入物能够用自体人造血细胞再生。研究人员观察到巨细胞病毒感染后强力的抗原特异性体液和T细胞反应，这能够控制病毒的复制。只植入肺的小鼠和骨髓/肝/胸腺-肺人源化小鼠显著增加了可在体内研究的人病原体的数量，从而能够促进治疗的体内测试。
据了解，当前人源化小鼠模型的主要限制是它们主要能够分析感染造血细胞的人特异性病原体。然而，大多数人类病原体靶向其他细胞类型，包括上皮细胞、内皮细胞和间充质细胞。
附：英文原文
Title: Precision mouse models with expanded tropism for human pathogens
Author: Angela Wahl, Chandrav De, Maria Abad Fernandez, Erik M. Lenarcic, Yinyan Xu, Adam S. Cockrell, Rachel A. Cleary, Claire E. Johnson, Nathaniel J. Schramm, Laura M. Rank, Isabel G. Newsome, Heather A. Vincent, Wes Sanders, Christian R. Aguilera-Sandoval, Allison Boone, William H. Hildebrand, Paul A. Dayton, Ralph S. Baric, Raymond J. Pickles, Miriam Braunstein, Nathaniel J. Moorman, Nilu Goonetilleke, J. Victor Garcia
Issue&Volume: 2019-08-26
Abstract: A major limitation of current humanized mouse models is that they primarily enable the analysis of human-specific pathogens that infect hematopoietic cells. However, most human pathogens target other cell types, including epithelial, endothelial and mesenchymal cells. Here, we show that implantation of human lung tissue, which contains up to 40 cell types, including nonhematopoietic cells, into immunodeficient mice (lung-only mice) resulted in the development of a highly vascularized lung implant. We demonstrate that emerging and clinically relevant human pathogens such as Middle East respiratory syndrome coronavirus, Zika virus, respiratory syncytial virus and cytomegalovirus replicate in vivo in these lung implants. When incorporated into bone marrow/liver/thymus humanized mice, lung implants are repopulated with autologous human hematopoietic cells. We show robust antigen-specific humoral and T-cell responses following cytomegalovirus infection that control virus replication. Lung-only mice and bone marrow/liver/thymus-lung humanized mice substantially increase the number of human pathogens that can be studied in vivo, facilitating the in vivo testing of therapeutics.
DOI: 10.1038/s41587-019-0225-9
Source: https://www.nature.com/articles/s41587-019-0225-9
Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex
本期文章：《自然—生物技术》：Online/在线发表
