近日，一项发表于国际杂志Circulation上的研究论文中，来自休斯顿卫理公会研究所的研究人员成功地将人类机体的疤痕细胞转化成为血管细胞，该研究发现或为开发修复损伤组织的疗法以及改善机体组织供血、氧气、营养的新方法提供了一定的帮助和希望。

John Cooke教授表示，据我们所知，本文研究是首次利用小分子和蛋白来完成治疗细胞类型的分化转移，在特殊情况下我们就可以将成纤维细胞转化成为所需的细胞类型。文章中研究者首先将成纤维细胞暴露于多聚胞苷酸(polyinosinic-polycytidylic acid，poly I：C)中，双链RNA分子的一小部分会结合宿主细胞的TLR3(toll样受体3)来“哄骗”细胞好像针对病毒攻击那样产生反应;在2012年发表在Cell上的一篇研究文章中，Cooke教授就揭示了成纤维细胞对病毒攻击的反应，在利用poly I：C处理成纤维细胞后，研究者观察到了细胞核染色质的重新组装，这种组装可以使得之前关闭的基因重新表达，随后利用诸如VEGF等因子对成纤维细胞进行处理，就可以将少量分化的细胞转化成为内皮细胞。

在这项研究中，研究者报道可以将2%的成纤维细胞转化成为内皮细胞，这种比例可以和其它利用病毒及基因疗法得到的转化率等同，但Cooke补充道，目前我们可以使得转化率高达15%;我们并不想让所有的成纤维细胞都发生转化，因为成纤维细胞还发挥着非常重要的作用，文章中我们只是促进部分的疤痕细胞转化成为血管细胞，从而为损伤组织提供血液供给。

随着研究的深入，研究者将已经转化的人类细胞(血管细胞)引入到免疫缺陷的小鼠机体中，这些小鼠下肢的血液流动较差，研究者发现人类的血管细胞可以增加小鼠下肢的血管数量，有效改善其血液循环。这些血管细胞可以自发形成血管组织;下一步研究人员想去研究是否其可以拯救受伤的动物，如果该疗法可以通过增加受损组织的血液流动从而达到治愈的目的，那么其或许就为开发治疗局部缺血等一系列疾病的新型疗法提供希望。

原文摘要：

Transdifferentiation of human Fibroblasts to Endothelial Cells: Role of Innate Immunity

Nazish Sayed; Wing Tak Wong; Frank Ospino; Shu Meng; Jieun Lee; Arshi Jha; Philip Dexheimer; Bruce J. Aronow; John P. Cooke

Background—Cell fate is fluid, and may be altered experimentally by the forced expression of master regulators mediating cell lineage. Such reprogramming has been achieved using viral vectors encoding transcription factors. We recently discovered that the viral vectors are more than passive vehicles for transcription factors, as they participate actively in the process of nuclear reprogramming to pluripotency by increasing epigenetic plasticity. Based on this recognition, we hypothesized that small molecule activators of toll-like receptor 3 (TLR3), together with external microenvironmental cues that drive EC specification, might be sufficient to induce transdifferentiation of fibroblasts into ECs (iECs). Methods and Results—We show that TLR3 agonist Poly I:C, combined with exogenous EC growth factors, transdifferentiated human fibroblasts into ECs. These iECs were comparable to HMVEC in immunohistochemical, genetic and functional assays, including the ability to form capillary-like structures and to incorporate acetylated-LDL. Furthermore, iECs significantly improved limb perfusion and neovascularization in the murine ischemic hindlimb. Finally, using genetic knockdown studies, we find that the effective transdifferentiation of human fibroblasts to endothelial cells requires innate immune activation. Conclusions—This study suggests that manipulation of innate immune signaling may be generally used to modify cell fate. As similar signaling pathways are activated by damage associated molecular patterns, epigenetic plasticity induced by innate immunity may play a fundamental role in transdifferentiation during wound healing and regeneration. Finally, this study is a first step toward development of a small molecule strategy for therapeutic transdifferentiation for vascular disease.（doi:10.1161/CIRCULATIONAHA.113.007394）

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