An overview of reprogramming approaches to derive integration-free induced pluripotent stem cells for prospective biomedical applications

The remarkable discovery of the derivation of induced pluripotent stem cells (iPSCs) heralded the development of a new technological platform for therapeutic applications in drug screening and discovery, disease modeling, patient-specific personalized medicine, and studying human developmental biology. Over the span of 10 years, numerous research groups have taken various initiatives to circumvent the limitations posed by the use of integrating approaches (γ-retrovirus and lentivirus) in the generation of iPSCs. The nonintegrating approaches employed in the derivation of iPSCs overcome the risk of chromosomal integration, insertional mutagenesis, and tumor formation posed by integrating approaches, thereby enhancing the scope of these cells for translational research. This chapter cornerstones the current state of iPSC generation, explicitly focusing on promising reprogramming strategies such as nonintegrating viral (Sendai virus vectors) and nonviral (episomal vectors, mRNAs, microRNAs, recombinant proteins, and small molecules) approaches, providing an insight into the basic nuances used for the derivation of integration-free iPSCs. To generate clinical-grade human iPSCs, reprogramming strategies that do not involve integration into the somatic cell genome and alteration of the same are preferred. Therefore, understanding these integration-free approaches will take us a step closer to developing safe techniques to derive clinical-grade human iPSCs for various biomedical applications.