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.

诱导多能干（iPS）细胞的基因编辑代表了治疗艾滋病毒的一条有希望的途径。然而，在将这种方法应用于临床之前，仍然存在某些挑战。其中，需要实现体外基因编辑细胞的体内植入。在这项研究中，体外衍生自经过基因修饰携带 CCR5Δ32 突变等位基因的 iPS 细胞的 CD34 ⁺细胞并未移植到人源化免疫缺陷小鼠中。然而，从畸胎瘤中分离出的 CD34 ⁺细胞是由所有实验中植入的这些经过基因编辑的 iPS 细胞在体内产生的。这些 CD34 ⁺细胞还在小鼠体内产生外周血单核细胞，当在细胞培养物中接种 HIV 时，这些细胞对 HIV R5 嗜性分离株具有抵抗力。这项研究表明畸胎瘤可以提供一个环境，帮助评估来自转基因 iPS 细胞的 CD34 ^{+细胞的体外植入潜力。}结果进一步证实了使用基因工程 iPS 细胞衍生出抗 HIV 的可移植造血干细胞作为治疗 HIV 的方法的可能性。