Müller Lars U W, Daley George Q, Williams David A
Department of Medicine, Division of Pediatric Hematology Oncology, Children's Hospital Boston, Boston, Massachusetts 02115, USA.
Mol Ther. 2009 Jun;17(6):947-53. doi: 10.1038/mt.2009.72. Epub 2009 Mar 31.
The concept of reversing the characteristics of differentiated tissues to pluripotency through reprogramming was introduced over 50 years ago in the first somatic cell nuclear transfer (SCNT) experiments. More recently, direct reprogramming of differentiated somatic cells by gene transfer of a small number of defined transcription factors has been shown to yield cells that are indistinguishable from inner cell mass-derived embryonic stem (ES) cells. These cells, termed induced pluripotent stem (iPS) cells, offer exciting possibilities for studying mechanism of pluripotency, establishing models for disease-specific investigations, and enabling future applications in regenerative medicine. In this review, we discuss the basic foundation of reestablishing pluripotency and recent progress toward enhancing the efficiency and safety of the process through optimization of the reprogramming factor combination, identification of small molecules that augment efficiency, and assessment of distinct target cells in reprogramming efficiency. We also highlight recent advances that eliminate stable genetic modification from the reprogramming process, and summarize preclinical models that provide proof-of-concept for ES/iPS cell-based regenerative medicine.
50多年前，在首次体细胞细胞核移植（SCNT）实验中引入了通过重编程将分化组织的特性逆转至多能性的概念。最近，通过导入少量特定转录因子进行基因转移直接重编程分化的体细胞，已被证明可以产生与源自内细胞团的胚胎干细胞（ES细胞）无法区分的细胞。这些细胞被称为诱导多能干细胞（iPS细胞），为研究多能性机制、建立疾病特异性研究模型以及在再生医学中的未来应用提供了令人兴奋的可能性。在这篇综述中，我们讨论了重新建立多能性的基础，以及通过优化重编程因子组合、鉴定提高效率的小分子和评估重编程效率方面不同的靶细胞，在提高该过程的效率和安全性方面的最新进展。我们还强调了在重编程过程中消除稳定基因修饰的最新进展，并总结了为基于ES/iPS细胞的再生医学提供概念验证的临床前模型。
