Induced Pluripotent Stem Cells and Their Application to Personalized Therapy

© 2011 Elsevier B.V. All rights reserved. Human-induced pluripotent cells (hiPSCs) are derived by reprogramming somatic cells using a specific cocktail of transcription factors to a self-renewing, pluripotent state that is similar to human embryonic stem cells (hESCs). This technology enables the derivation of pluripotent cells from any individual/patient, which can then be used for study in the context of the genetic background of the patient, and also potentially for personalized cell replacement therapy. In one fell swoop, this overcomes the double hurdle of transplant histo-incompatibility and ethical controversies surrounding hESCs. However, there is an enormous amount of work to be done before any hiPSC-derived cells could ever be used clinically. The entire process of reprogramming, expansion, subsequent genetic manipulation, differentiation, and delivery and monitoring of transplanted cells would need to be as risk free and standardized as possible. This entails good manufacturing practice, preferably xeno-free, protocols that minimize insertional mutagenesis during reprogramming/genetic manipulation, minimize and monitor karyotype changes at high resolution, and minimize the risk of undifferentiated cells being accidentally transplanted along with the differentiated progeny. Safety nets, for example, suicide gene strategies, need to be included to enable elimination of any wayward cells after transplantation. While this long road is being walked, hiPSCs will, meanwhile, be of enormous value for basic research and drug discovery.