A new humanized pig model

IF 3.9 3区农林科学 Q1 VETERINARY SCIENCES

Lab Animal Pub Date : 2025-07-30 DOI:10.1038/s41684-025-01591-8

Alexandra Le Bras

{"title":"A new humanized pig model","authors":"Alexandra Le Bras","doi":"10.1038/s41684-025-01591-8","DOIUrl":null,"url":null,"abstract":"Humanized mice engrafted with human hematopoietic stem and progenitor cells (HSPCs) are valuable models for exploring human immunology. However, the small size and short lifespan of the mouse models limit their translational value. Pigs are suitable large animal models for preclinical research, but existing immunodeficient pig models show limited human HSPC engraftment and multilineage differentiation. A new study reports the development of an immunodeficient pig model that supports robust human HSPC engraftment and blood cell formation, offering a valuable preclinical tool for studying human immunology. The researchers used CRISPR-Cas9 technology to inactivate RAG1 and IL2RG in Bama pig fibroblasts and generated the immunodeficient pigs via somatic cell nuclear transfer and embryo transfer. The team also deleted CD47, a gene encoding a cell surface protein that regulates macrophage-mediated phagocytosis with the aim of preventing rejection of human cells by pig macrophages. Using multiple approaches to characterize human cell development in the engineered pigs, the researchers found that the triple-knockout pigs (RAG2/IL2RG/CD47) showed long-term human HSPC engraftment in the bone marrow, robust thymopoiesis and T cell development in the thymus, and repopulation with multilineage human hematopoietic cells throughout tissues.Original reference: Hu, Z. et al. Nat. Biomed. Eng. https://doi.org/10.1038/s41551-025-01397-6 (2025)","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"5 1","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lab Animal","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1038/s41684-025-01591-8","RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Humanized mice engrafted with human hematopoietic stem and progenitor cells (HSPCs) are valuable models for exploring human immunology. However, the small size and short lifespan of the mouse models limit their translational value. Pigs are suitable large animal models for preclinical research, but existing immunodeficient pig models show limited human HSPC engraftment and multilineage differentiation. A new study reports the development of an immunodeficient pig model that supports robust human HSPC engraftment and blood cell formation, offering a valuable preclinical tool for studying human immunology. The researchers used CRISPR-Cas9 technology to inactivate RAG1 and IL2RG in Bama pig fibroblasts and generated the immunodeficient pigs via somatic cell nuclear transfer and embryo transfer. The team also deleted CD47, a gene encoding a cell surface protein that regulates macrophage-mediated phagocytosis with the aim of preventing rejection of human cells by pig macrophages. Using multiple approaches to characterize human cell development in the engineered pigs, the researchers found that the triple-knockout pigs (RAG2/IL2RG/CD47) showed long-term human HSPC engraftment in the bone marrow, robust thymopoiesis and T cell development in the thymus, and repopulation with multilineage human hematopoietic cells throughout tissues.

Original reference: Hu, Z. et al. Nat. Biomed. Eng. https://doi.org/10.1038/s41551-025-01397-6 (2025)

查看原文本刊更多论文

一种新的人性化猪模型

移植人造血干细胞和祖细胞（HSPCs）的人源化小鼠是探索人类免疫学的重要模型。然而，小鼠模型的小尺寸和短寿命限制了它们的转化价值。猪是适合临床前研究的大型动物模型，但现有的免疫缺陷猪模型显示有限的人类HSPC植入和多谱系分化。一项新的研究报告了一种免疫缺陷猪模型的发展，该模型支持强大的人类HSPC植入和血细胞形成，为研究人类免疫学提供了有价值的临床前工具。研究人员利用CRISPR-Cas9技术灭活巴马猪成纤维细胞中的RAG1和IL2RG，通过体细胞核移植和胚胎移植产生免疫缺陷猪。该团队还删除了CD47，这是一种编码细胞表面蛋白的基因，该蛋白调节巨噬细胞介导的吞噬作用，目的是防止人类细胞被猪巨噬细胞排斥。研究人员使用多种方法来表征工程猪的人类细胞发育，发现三敲除猪（RAG2/IL2RG/CD47）在骨髓中长期植入人类HSPC，在胸腺中表现出强大的胸腺生成和T细胞发育，并在整个组织中重新填充了多系人类造血细胞。原文献：Hu， Z.等。Nat,生物医学。Eng。https://doi.org/10.1038/s41551 - 025 - 01397 - 6 (2025)

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Lab Animal 农林科学-兽医学

CiteScore

0.60

自引率

2.90%

发文量

181

审稿时长

>36 weeks

期刊介绍： LabAnimal is a Nature Research journal dedicated to in vivo science and technology that improves our basic understanding and use of model organisms of human health and disease. In addition to basic research, methods and technologies, LabAnimal also covers important news, business and regulatory matters that impact the development and application of model organisms for preclinical research. LabAnimal's focus is on innovative in vivo methods, research and technology covering a wide range of model organisms. Our broad scope ensures that the work we publish reaches the widest possible audience. LabAnimal provides a rigorous and fair peer review of manuscripts, high standards for copyediting and production, and efficient publication.