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通过小生境工程来造血

摘要 : 重编程体细胞来生成造血干细胞是非常困难的。美国威尔康乃尔医学院的研究人员发明了一种新型的造血方法。这种自体造血方法对于遗传性和获得性血液病的治疗具有可能的临床应用潜力。相关文章发表于2014年7月2日的《Nature》杂志上。
通过小生境工程来造血

Shahin Rafii及同事介绍了一个方法,它利用四个转录因子连同一个人造无血清血管小生境平台,来将人内皮细胞(它们组成血管内壁)重新编程为具有长期多能祖细胞活性的造血细胞。

这样获得的重新编程的血细胞一旦植入小鼠模型中,能够循环、寻的和嫁接进骨髓中,重建造血功能。这种自体造血方法对于遗传性和获得性血液病的治疗具有可能的临床应用潜力。

原文摘要:

Reprogramming human endothelial cells to haematopoietic cells requires vascular induction

Vladislav M. Sandler, Raphael Lis, Ying Liu, Alon Kedem, Daylon James, Olivier Elemento,Jason M. Butler, Joseph M. Scandura & Shahin Rafii

Generating engraftable human haematopoietic cells from autologous tissues is a potential route to new therapies for blood diseases. However, directed differentiation of pluripotent stem cells yields haematopoietic cells that engraft poorly. Here, we have devised a method to phenocopy the vascular-niche microenvironment of haemogenic cells, thereby enabling reprogramming of human endothelial cells into engraftable haematopoietic cells without transition through a pluripotent intermediate. Highly purified non-haemogenic human umbilical vein endothelial cells or adult dermal microvascular endothelial cells were transduced with the transcription factors FOSB, GFI1, RUNX1and SPI1 (hereafter referred to as FGRS), and then propagated on serum-free instructive vascular niche monolayers to induce outgrowth of haematopoietic colonies containing cells with functional and immunophenotypic features of multipotent progenitor cells (MPPs). These endothelial cells that have been reprogrammed into human MPPs (rEC-hMPPs) acquire colony-forming-cell potential and durably engraft into immune-deficient mice after primary and secondary transplantation, producing long-term rEC-hMPP-derived myeloid (granulocytic/monocytic, erythroid, megakaryocytic) and lymphoid (natural killer and B cell) progenies. Conditional expression of FGRS transgenes, combined with vascular induction, activates endogenous FGRS genes, endowing rEC-hMPPs with a transcriptional and functional profile similar to that of self-renewing MPPs. Our approach underscores the role of inductive cues from the vascular niche in coordinating and sustaining haematopoietic specification and may prove useful for engineering autologous haematopoietic grafts to treat inherited and acquired blood disorders.

对应Nature杂志: 2014年7月17日Nature杂志精选

来源: Nature中文 浏览次数:53

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