Stem Cells：科学家首次将人类皮肤细胞成功转化为白细胞

       近日，发表在国际杂志Stem Cells上的一篇研究论文中，来自索尔克研究所的研究人员通过研究首次将人类的皮肤细胞成功转化为机体可移植的白细胞，众所周知白细胞是机体免疫系统的“战士”，其可以保护机体抵御感染和外来入侵者。

      研究者Juan Carlos Izpisua Belmont表示，这项研究或为开发新型疗法为机体引入新型白细胞来治疗癌症等疾病提供新的思路和希望。目前研究者们在小鼠机体中研究发现转化成为白细胞的过程非常迅速且安全，该方法绕过了长期存在的研究障碍，为开发人类细胞的重组再生疗法提供了新的线索。

      由诱导多能干细胞产生的血细胞往往不能够移植入器官或骨髓中，而且其也有可能引发肿瘤产生；而本文研究中研究者开发的这种名为间接谱系转化的新技术耗时仅需两周，并不会产生额外的肿瘤组织；研究者表示，我们会令皮肤细胞“忘掉”其自有的属性，然后让其转化为我们所需要的细胞类型，在这项研究中我们就让其成功转化成了白细胞。

      研究者Belmont开发的这种间接谱系转化技术可以用于制造人类的血管细胞，这种技术利用一种名为SOX2的分子，让其变得具有可塑性，即失去转变成特殊细胞类型的记忆，随后研究人员让名为miRNA125b的遗传因子诱导细胞转变成为白细胞。本文研究让研究人员未来成功进行干细胞移植治疗人类疾病又迈进了新的一步。

Stem Cells：科学家首次将人类皮肤细胞成功转化为白细胞

doi:10.1002/stem.1800
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Conversion of Human Fibroblasts into Monocyte-Like Progenitor Cells

Julian Pulecio1,‡,*, Emmanuel Nivet2,†,‡, Ignacio Sancho-Martinez2,‡, Marianna Vitaloni1, Guillermo Guenechea3, Yun Xia2, Leo Kurian2, Ilir Dubova2,3, Juan Bueren3, Leopoldo Laricchia-Robbio1 andJuan Carlos Izpisua Belmonte2

Reprogramming technologies have emerged as a promising approach for future regenerative medicine. Here we report on the establishment of a novel methodology allowing for the conversion of human fibroblasts into Hematopoietic Progenitor-like Cells (HPC) with macrophage differentiation potential. SOX2 overexpression in human fibroblasts, a gene found to be upregulated during hematopoietic reconstitution in mice, induced the rapid appearance of CD34+ cells with a concomitant upregulation of mesoderm-related markers. Profiling of Cord Blood hematopoietic progenitor cell populations identified miR-125b as a factor facilitating commitment of SOX2-generated CD34+ cells to immature hematopoietic-like progenitor cells with grafting potential. Further differentiation towards the monocytic lineage resulted in the appearance of CD14+ cells with functional phagocytic capacity. In vivo transplantation of SOX2/miR-125b-generated CD34+ cells facilitated the maturation of the engrafted cells towards CD45+ cells and ultimately the monocytic/macrophage lineage. Altogether, our results indicate that strategies combining lineage conversion and further lineage specification by in vivo or in vitro approaches could help to circumvent long-standing obstacles for the reprogramming of human cells into hematopoietic cells with clinical potential. Stem Cells 2014