Fit-For-All iPSC-Derived Cell Therapies and Their Evaluation in Humanized Mice With NK Cell Immunity.
Fit-For-All iPSC-Derived Cell Therapies and Their Evaluation in Humanized Mice With NK Cell Immunity.
复制标题
DOI：
10.3389/fimmu.2021.662360
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Sugimoto N
中科院分区：
文献类型：
--
作者：
Flahou C;Morishima T;Takizawa H;Sugimoto N
人诱导多能干细胞（iPSCs）可以无限扩增并分化为几乎所有的细胞类型。此外，它们易于基因操作，而且由于它们是由体细胞建立的，因此基本上可以从任何人身上建立。基于这些特点，iPSCs作为组织移植、输血和癌症免疫治疗的细胞来源得到了广泛的研究，相关的临床试验也已经开始。从免疫匹配的角度来看，自体iPSCs原则上是完全兼容的，但也需要较长的时间才能达到最终产品，成本高，人与人之间的差异阻碍了它们的普遍使用。因此，经过认证的免疫原性降低的iPSCs有望成为现成的来源，例如由人类白细胞抗原（HLA）纯合子个体制成的iPSCs或经过HLA修饰的iPSCs。用人类免疫系统（HIS）重组免疫缺陷小鼠进行临床前试验是评估人类对ipsc来源细胞的同种异体反应的重要工具。特别是，用人类T细胞和人类自然杀伤（NK）细胞重组的HIS小鼠被认为是至关重要的。NK细胞攻击不表达自身HLA I类的所谓“缺失自我”细胞，包括仅表达一种等位基因类型的HLA纯合细胞和HLA耗尽细胞。然而，传统的HIS小鼠缺乏足够的重组人类NK细胞进行这些测试。已经开发了几种方法来克服这一问题，包括使用增强NK细胞扩增的细胞因子，如IL-2和IL-15，使用表达这些细胞因子的载体，以及通过基因操作来表达细胞因子或增强表达il - 15r - α的人髓细胞的重建。利用增强的人类NK细胞重构的HIS小鼠，研究了对hla纯合细胞和hla缺失细胞的同种异体反应。然而，大多数研究使用hla下调的肿瘤细胞作为靶细胞，并从HIS小鼠中纯化人细胞后进行体外测试。在这篇综述中，我们概述了ipsc在细胞治疗中的现状，降低其免疫原性潜力的策略，然后阐述了重组NK细胞在HIS小鼠中的发展，以及它们在评估未来通用hla工程ipsc衍生细胞中的应用。
Human induced pluripotent stem cells (iPSCs) can be limitlessly expanded and differentiated into almost all cell types. Moreover, they are amenable to gene manipulation and, because they are established from somatic cells, can be established from essentially any person. Based on these characteristics, iPSCs have been extensively studied as cell sources for tissue grafts, blood transfusions and cancer immunotherapies, and related clinical trials have started. From an immune-matching perspective, autologous iPSCs are perfectly compatible in principle, but also require a prolonged time for reaching the final products, have high cost, and person-to-person variation hindering their common use. Therefore, certified iPSCs with reduced immunogenicity are expected to become off-the-shelf sources, such as those made from human leukocyte antigen (HLA)-homozygous individuals or genetically modified for HLA depletion. Preclinical tests using immunodeficient mice reconstituted with a human immune system (HIS) serve as an important tool to assess the human alloresponse against iPSC-derived cells. Especially, HIS mice reconstituted with not only human T cells but also human natural killer (NK) cells are considered crucial. NK cells attack so-called “missing self” cells that do not express self HLA class I, which include HLA-homozygous cells that express only one allele type and HLA-depleted cells. However, conventional HIS mice lack enough reconstituted human NK cells for these tests. Several measures have been developed to overcome this issue including the administration of cytokines that enhance NK cell expansion, such as IL-2 and IL-15, the administration of vectors that express those cytokines, and genetic manipulation to express the cytokines or to enhance the reconstitution of human myeloid cells that express IL15R-alpha. Using such HIS mice with enhanced human NK cell reconstitution, alloresponses against HLA-homozygous and HLA-depleted cells have been studied. However, most studies used HLA-downregulated tumor cells as the target cells and tested in vitro after purifying human cells from HIS mice. In this review, we give an overview of the current state of iPSCs in cell therapies, strategies to lessen their immunogenic potential, and then expound on the development of HIS mice with reconstituted NK cells, followed by their utilization in evaluating future universal HLA-engineered iPSC-derived cells.
登录
查看更多内容
DOI：
10.1084/jem.187.5.813
发表时间：
1998-03-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Borrego F;Ulbrecht M;Weiss EH;Coligan JE;Brooks AG
通讯作者：
Brooks AG
影响因子：
30.5
作者：
Allen, Todd M.;Brehm, Michael A.;PrabhuDas, Mercy
通讯作者：
PrabhuDas, Mercy
影响因子：
64.8
作者：
Braud, VM;Allan, DSJ;McMichael, AJ
通讯作者：
McMichael, AJ
影响因子：
6
作者：
Benabdallah B;Désaulniers-Langevin C;Goyer ML;Colas C;Maltais C;Li Y;Guimond JV;Tremblay JP;Haddad E;Beauséjour C
通讯作者：
Beauséjour C
影响因子：
7.3
作者：
Benabdallah, Basma;Desaulniers-Langevin, Cynthia;Beausejour, Christian
通讯作者：
Beausejour, Christian