A humanized mouse model to study human immune response in xenotransplantation
A humanized mouse model to study human immune response in xenotransplantation
复制标题
研究异种移植中人类免疫反应的人源化小鼠模型
DOI：
10.1016/s1499-3872(12)60213-6
复制
发表时间：
2012-10-15
影响因子：
3.3
通讯作者：
Yi, Shounan
中科院分区：
文献类型：
--
作者：
Ji, Ming;Jin, Xi;Yi, Shounan
背景：异种移植作为患者治疗选择临床应用的一个主要障碍是 T 细胞介导的排斥反应。基于体内异种移植耐受或排斥的实验啮齿动物模型的研究提供了有关 T 细胞免疫反应在异种移植中的作用的有用信息。然而，并非所有在啮齿类动物身上观察到的现象都忠实地再现了人类的情况。本研究旨在建立异种移植的人源化小鼠模型，模拟人类免疫系统背景下的异种移植排斥反应。方法：将新生猪胰岛细胞簇（NICC）移植到NOD-SCID IL2r gamma（-/-）小鼠中，然后重建人外周血单核细胞（PBMC）。通过流式细胞术和组织学分析证实了人白细胞植入和胰岛异种移植排斥。结果：在缺乏人PBMC的情况下，猪NICC移植到NOD-SCID IL2r gamma(-/-)小鼠体内显示出良好的移植物完整性和内分泌功能。人 PBMC 在 NOD-SCID IL2r gamma(-/-) 小鼠中表现出高水平的植入。用人 PBMC 重建 NICC 受体 NOD-SCID IL2r gamma(-/-) 小鼠，导致 NICC 异种移植物以 PBMC 数量依赖性方式快速破坏。结论：人 PBMC 重建的 NOD-SCID IL2r gamma(-/-) 小鼠为研究异种移植中的人类免疫反应提供了理想的模型。基于这种人源化小鼠模型的研究将为改善临床异种移植的结果提供见解。 （肝胆胰疾病国际杂志 2012 年；11：494-498）
BACKGROUND: A major barrier to the clinical application of xenotransplantation as a treatment option for patients is T cell-mediated rejection. Studies based on experimental rodent models of xenograft tolerance or rejection in vivo have provided useful information about the role of T cell immune response in xenotransplantation. However not all observations seen in rodents faithfully recapitulate the human situation. This study aimed to establish a humanized mouse model of xenotransplantation, which mimics xenograft rejection in the context of the human immune system.METHODS: NOD-SCID IL2r gamma(-/-) mice were transplanted with neonatal porcine islet cell clusters (NICC) followed by reconstitution of human peripheral blood mononuclear cells (PBMC). Human leukocyte engraftment and islet xenograft rejection were confirmed by flow cytometric and histological analyses.RESULTS: In the absence of human PBMC, porcine NICC transplanted into NOD-SCID IL2r gamma(-/-) mice revealed excellent graft integrity and endocrine function. Human PBMC demonstrated a high level of engraftment in NOD-SCID IL2r gamma(-/-) mice. Reconstitution of NICC recipient NOD-SCID IL2r gamma(-/-) mice with human PBMC led to the rapid destruction of NICC xenografts in a PBMC number-dependent manner.CONCLUSIONS: Human PBMC-reconstituted NOD-SCID IL2r gamma(-/-) mice provide an ideal model to study human immune responses in xenotransplantation. Studies based on this humanized mouse model will provide insight for improving the outcomes of clinical xenotransplantation. (Hepatobiliary Pancreat Dis Int 2012;11:494-498)