In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells
In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells
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DOI：
10.1182/blood-2012-06-434407
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发表时间：
2013-02-21
期刊：
影响因子：
20.3
通讯作者：
Tenen, Daniel G.
中科院分区：
文献类型：
--
作者：
Amabile, Giovanni;Welner, Robert S.;Tenen, Daniel G.
谱系限制性细胞可以通过4种转录因子的过表达重编程为多能状态，称为诱导多能干细胞（iPS）。iPS细胞类似于人类胚胎干细胞（hES），具有产生人体所有细胞（包括血细胞）的能力。然而，这一过程效率极低，迄今为止在将iPS分化为造血干细胞（HSC）方面一直不成功。我们假设，iPS细胞，注入NOD。Cg-Prkdc（scid）Il 2 rg（tm 1 Wjl）/SzJ免疫功能低下（NSG）小鼠在畸胎瘤形成过程中可产生造血干/祖细胞（HSPCs）。在这里，我们报告了一种新的体内系统，其中人iPS细胞分化畸胎瘤内衍生功能性骨髓和淋巴样细胞。类似地，HSPC可以从畸胎瘤实质中分离，并且当移植到免疫缺陷小鼠中时重建人免疫系统。我们的数据提供了证据表明，在体内产生患者定制的细胞是可行的，提供的材料，可能是有用的移植，人抗体的产生，和药物筛选应用。
Lineage-restricted cells can be reprogrammed to a pluripotent state known as induced pluripotent stem (iPS) cells through overexpression of 4 transcription factors. iPS cells are similar to human embryonic stem (hES) cells and have the same ability to generate all the cells of the human body, including blood cells. However, this process is extremely inefficient and to date has been unsuccessful at differentiating iPS into hematopoietic stem cells (HSCs). We hypothesized that iPS cells, injected into NOD. Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ immunocompromised (NSG) mice could give rise to hematopoietic stem/progenitor cells (HSPCs) during teratoma formation. Here, we report a novel in vivo system in which human iPS cells differentiate within teratomas to derive functional myeloid and lymphoid cells. Similarly, HSPCs can be isolated from teratoma parenchyma and reconstitute a human immune system when transplanted into immunodeficient mice. Our data provide evidence that in vivo generation of patient customized cells is feasible, providing materials that could be useful for transplantation, human antibody generation, and drug screening applications.