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Cocktail of chemical compounds robustly promoting cell reprogramming protects liver against acute injury

机译:化合物鸡尾酒可强烈促进细胞重编程保护肝脏免受急性损伤

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摘要

Tissue damage induces cells into reprogramming-like cellular state, which contributes to tissue regeneration. However, whether factors promoting the cell reprogramming favor tissue regeneration remains elusive. Here we identified combination of small chemical compounds including drug cocktails robustly promoting in vitro cell reprogramming. We then administrated the drug cocktails to mice with acute liver injuries induced by partial hepatectomy or toxic treatment. Our results demonstrated that the drug cocktails which promoted cell reprogramming in vitro improved liver regeneration and hepatic function in vivo after acute injuries. The underlying mechanism could be that expression of pluripotent genes activated after injury is further upregulated by drug cocktails. Thus our study offers proof-of-concept evidence that cocktail of clinical compounds improving cell reprogramming favors tissue recovery after acute damages, which is an attractive strategy for regenerative purpose.Electronic supplementary materialThe online version of this article (doi:10.1007/s13238-017-0373-y) contains supplementary material, which is available to authorized users.
机译:组织损伤诱导细胞进入重编程样细胞状态,这有助于组织再生。但是,促进细胞重编程的因素是否有利于组织再生仍然难以捉摸。在这里,我们确定了包括药物混合物在内的小化学化合物的组合,可强有力地促进体外细胞重编程。然后,我们对部分肝切除术或中毒治疗引起的急性肝损伤的小鼠给予药物鸡尾酒治疗。我们的结果表明,在急性损伤后,促进体外细胞重编程的药物混合物可改善体内肝脏的再生和肝功能。潜在的机制可能是药物混合物进一步上调了损伤后激活的多能基因的表达。因此,我们的研究提供了概念验证性证据,表明临床化合物的混合物改善了细胞的重新编程能力,有利于急性损伤后的组织恢复,这对于再生目的是有吸引力的策略。电子补充材料本文的在线版本(doi:10.1007 / s13238-017) -0373-y)包含补充材料,授权用户可以使用。

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