Overcoming barriers to the clinical utilization of iPSCs: reprogramming efficiency, safety and quality

Differentiated cells can be reprogrammed into pluripotent stem cells, known as "induced pluripotent stem cells" (iPSCs), through the overexpression of defined transcription factors. The creation of iPSC lines has opened new avenues for patient-specific cell replacement therapies for regenerative medicine. However, the clinical utilization of iPSCs is largely impeded by two limitations. The first limitation is the low efficiency of iPSCs generation from differentiated cells. The second limitation is that many iPSC lines are not authentically pluripotent, as many cell lines inefficiently differentiate into differentiated cell types when they are tested for their ability to complement embryonic development. Thus, the "quality" of iPSCs must be increased if they are to be differentiated into specialized cell types for cell replacement therapies. Overcoming these two limitations is paramount to facilitate the widespread employment of iPSCs for therapeutic purposes. Here, we summarize recent progress made in strategies enabling the efficient production of high-quality iPSCs, including choice of reprogramming factors, choice of target cell type, and strategies to improve iPSC quality.