Abstract
Induced pluripotent stem cells (iPSCs) hold great potential for regenerative medicine, yet their implementation in the clinic still seems far out of reach due to concerns about their safety. The development of safe and efficient reprogramming methods is a critical step towards clinical application of iPSCs. Recently, much progress has been made in the technology of generating iPSCs that are free of integrated transgenes. The newly developed methods improve genome integrity of iPSCs and will likely replace virus-based reprogramming in the future. Here, we review the recent technological advancements of transgene-free reprogramming and discuss the challenges of ensuring genome integrity of iPSCs.