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Generation and applications of iPSCs. a Various methods and approaches are used to convert somatic cells into iPSCs. Integrative methods such as integrative viruses and vectors provide the highest reprogramming efficiency but the lowest safety. In contrast, non-integrative approaches such as the use of small molecules and microRNAs tend to have a less reprogramming efficiency. Notably, episomal vectors, which do not integrate with the host cell’s genome, appear to provide both a high efficiency of iPSC generation and sufficient degree of safety. Although all the illustrated approaches could potentially be used to produce iPSCs for applications such as basic research, drug screening, and disease modeling, genomic integration should be avoided for generation of clinical-grade iPSCs. b Because of immortality and immense differentiation potential, iPSCs have all the potential biomedical applications of ESCs. They can be used to model pluripotency and multi-lineage differentiation in vitro, screen and discover new drugs, and establish disease models in a dish. iPSCs also hold a great potential to be used for replacing diseased or lost tissues, which needs specific considerations to provide safe, clinical-grade cells for transplantation into patients