Tang Yuewen, Cheng Lin
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Protein Cell. 2017 Apr;8(4):273-283. doi: 10.1007/s13238-017-0373-y. Epub 2017 Feb 11.
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.
组织损伤会诱导细胞进入类似重编程的细胞状态，这有助于组织再生。然而，促进细胞重编程的因素是否有利于组织再生仍不清楚。在这里，我们鉴定出了包括药物组合在内的小分子化合物组合，其能强有力地促进体外细胞重编程。然后，我们将这些药物组合给予通过部分肝切除术或毒性处理诱导急性肝损伤的小鼠。我们的结果表明，在体外促进细胞重编程的药物组合在急性损伤后能改善体内肝脏再生和肝功能。潜在机制可能是损伤后激活的多能基因的表达被药物组合进一步上调。因此，我们的研究提供了概念验证证据，即改善细胞重编程的临床化合物组合有利于急性损伤后的组织恢复，这是一种用于再生目的的有吸引力的策略。
