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人源化小鼠中T细胞隔室的从头构建
作者:小柯机器人 发布时间:2022/9/8 17:00:04

美国卡内基梅隆大学卡内基梅隆大学团队近期取得重要工作进展,他们发现利用诱导多能干细胞来源胸腺类器官移植人源化小鼠模型,可以重新生成T细胞隔室。该项研究成果2022年9月5日在线发表于《自然—方法学》杂志上。

研究人员描述了来自诱导型多能干细胞(iPSC-胸腺)的人类胸腺类器官的组织工程,它可以支持从头生成多种功能性人类T细胞群。移植iPSC来源胸腺的hu小鼠的T细胞可以介导细胞和体液免疫反应,包括对T细胞受体参与产生强烈的促炎反应、抑制同种异体移植瘤的生长和促进有效的Ig类型转换。他们的研究结果表明,移植iPSC胸腺的hu小鼠可以作为一种新的动物模型来研究人类T细胞介导的免疫,并加速将动物研究结果转化为临床。

据介绍,造血人源化(hu)小鼠是模拟人体免疫系统作用的强大工具,广泛用于临床前研究和药物开发。然而,在hu小鼠中产生功能性人类T细胞区室仍然具有挑战性,这主要是由于人类和小鼠胸腺之间的物种相关差异。虽然移植人类胎儿胸腺组织可以支持hu鼠的T细胞发育,但组织稀缺以及伦理问题限制了这一方法的广泛使用。

附:英文原文

Title: De novo construction of T cell compartment in humanized mice engrafted with iPSC-derived thymus organoids

Author: Zeleniak, Ann, Wiegand, Connor, Liu, Wen, McCormick, Catherine, K., Ravikumar, Alavi, Amir, Guan, Haonan, Bertera, Suzanne, Lakomy, Robert, Tajima, Asako, Cohen, Henry, Wong, Stephanie, Balikani, Lame, Mizerak, Benjamin, Bar-Joseph, Ziv, Trucco, Massimo, Banerjee, Ipsita, Fan, Yong

Issue&Volume: 2022-09-05

Abstract: Hematopoietic humanized (hu) mice are powerful tools for modeling the action of human immune system and are widely used for preclinical studies and drug discovery. However, generating a functional human T cell compartment in hu mice remains challenging, primarily due to the species-related differences between human and mouse thymus. While engrafting human fetal thymic tissues can support robust T cell development in hu mice, tissue scarcity and ethical concerns limit their wide use. Here, we describe the tissue engineering of human thymus organoids from inducible pluripotent stem cells (iPSC-thymus) that can support the de novo generation of a diverse population of functional human T cells. T cells of iPSC-thymus-engrafted hu mice could mediate both cellular and humoral immune responses, including mounting robust proinflammatory responses on T cell receptor engagement, inhibiting allogeneic tumor graft growth and facilitating efficient Ig class switching. Our findings indicate that hu mice engrafted with iPSC-thymus can serve as a new animal model to study human T cell-mediated immunity and accelerate the translation of findings from animal studies into the clinic.

DOI: 10.1038/s41592-022-01583-3

Source: https://www.nature.com/articles/s41592-022-01583-3

期刊信息

Nature Methods:《自然—方法学》,创刊于2004年。隶属于施普林格·自然出版集团,最新IF:28.467
官方网址:https://www.nature.com/nmeth/
投稿链接:https://mts-nmeth.nature.com/cgi-bin/main.plex