Upping the Ante: Recent Advances in Direct Reprogramming

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.