Efficient generation of human immune system rats using human CD34⁺ cells.

IF 5.9 2区医学 Q1 CELL & TISSUE ENGINEERING Stem Cell Reports Pub Date : 2024-09-10 Epub Date: 2024-08-15 DOI:10.1016/j.stemcr.2024.07.005

Séverine Ménoret, Florence Renart-Depontieu, Gaelle Martin, Kader Thiam, Ignacio Anegon

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Abstract

Human immune system (HIS) mice generated using human CD34⁺ hematopoietic stem cells serve as a pivotal model for the in vivo evaluation of immunotherapies for humans. Yet, HIS mice possess certain limitations. Rats, due to their size and comprehensive immune system, hold promise for translational experiments. Here, we describe an efficacious method for long-term immune humanization, through intrahepatic injection of hCD34⁺ cells in newborn immunodeficient rats expressing human SIRPα. In contrast to HIS mice and similar to humans, HIS rats showed in blood a predominance of T cells, followed by B cells. Immune humanization was also high in central and secondary lymphoid organs. HIS rats treated with the anti-human CD3 antibody were depleted of human T cells, and human cytokines were detected in sera. We describe for the first time a method to efficiently generate HIS rats. HIS rats have the potential to be a useful model for translational immunology.

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利用人体 CD34+ 细胞高效生成人体免疫系统大鼠。

利用人体 CD34+ 造血干细胞生成的人类免疫系统（HIS）小鼠是体内评估人类免疫疗法的重要模型。然而，人类免疫系统小鼠具有一定的局限性。大鼠因其体型和全面的免疫系统，为转化实验带来了希望。在这里，我们描述了一种长期免疫人源化的有效方法，即在表达人 SIRPα 的新生免疫缺陷大鼠肝内注射 hCD34+ 细胞。与 HIS 小鼠不同，HIS 大鼠的血液中 T 细胞占主导地位，其次是 B 细胞。中枢和次级淋巴器官的免疫人源化程度也很高。用抗人类 CD3 抗体治疗的 HIS 大鼠体内的人类 T 细胞被清除，血清中检测到人类细胞因子。我们首次描述了一种高效生成 HIS 大鼠的方法。HIS 大鼠有可能成为转化免疫学的有用模型。

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来源期刊

Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY

CiteScore

10.50

自引率

1.70%

发文量

200

审稿时长

28 weeks

期刊介绍： Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.