Genetically edited CD34+ cells derived from human iPS cells in vivo but not in vitro engraft and differentiate into HIV-resistant cells.
Genetically edited CD34+ cells derived from human iPS cells in vivo but not in vitro engraft and differentiate into HIV-resistant cells.
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来自人类 iPS 细胞的基因编辑 CD34 细胞在体内但不在体外移植并分化为 HIV 抗性细胞。
DOI：
10.1073/pnas.2102404118
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发表时间：
2021
影响因子：
11.1
通讯作者：
Levy,JayA
中科院分区：
文献类型：
--
作者：
Morvan,MaeligG;Teque,Fernando;Ye,Lin;Moreno,MaryE;Wang,Jiaming;VandenBerg,Scott;Stoddart,CherylA;Kan,YuetWai;Levy,JayA
诱导多能干细胞（iPS）的基因编辑代表了治愈艾滋病毒的一种有希望的途径。然而，在将这种方法引入临床之前，仍然存在一些挑战。其中，需要实现体外基因编辑细胞的体内植入。在本研究中，体外衍生自经遗传修饰以携带CCR 5 Δ32突变等位基因的iPS细胞的CD34+细胞未植入人源化免疫缺陷小鼠中。然而，从畸胎瘤中分离的CD34+细胞在体内从所有实验中移植的这些基因编辑的iPS细胞产生。这些CD34+细胞还在小鼠中产生外周血单核细胞，当在细胞培养物中接种HIV时，其对HIV R5嗜性分离株具有抗性。这项研究表明，畸胎瘤可以提供一个环境，可以帮助评估来自遗传修饰的iPS细胞的CD34+细胞在体外的植入潜力。这些结果进一步证实了使用基因工程iPS细胞来获得抗HIV的可移植造血干细胞作为HIV治愈方法的可能性。
Genetic editing of induced pluripotent stem (iPS) cells represents a promising avenue for an HIV cure. However, certain challenges remain before bringing this approach to the clinic. Among them, in vivo engraftment of cells genetically edited in vitro needs to be achieved. In this study, CD34+cells derived in vitro from iPS cells genetically modified to carry the CCR5Δ32 mutant alleles did not engraft in humanized immunodeficient mice. However, the CD34+cells isolated from teratomas generated in vivo from these genetically edited iPS cells engrafted in all experiments. These CD34+cells also gave rise to peripheral blood mononuclear cells in the mice that, when inoculated with HIV in cell culture, were resistant to HIV R5-tropic isolates. This study indicates that teratomas can provide an environment that can help evaluate the engraftment potential of CD34+cells derived from the genetically modified iPS cells in vitro. The results further confirm the possibility of using genetically engineered iPS cells to derive engraftable hematopoietic stem cells resistant to HIV as an approach toward an HIV cure.