Inducible pluripotent stem cells: Not quite ready for prime time?

Inducible pluripotent stem (iPS) cells, derived from somatic cells, offer a promising source of tissue precursors with potential comparable to human embryonic stem (hES) cells. These iPS cells could revolutionize the treatment of diseases like diabetes, spinal cord injuries, cardiovascular disease, and neurodegenerative diseases. A significant advantage of iPS cells is their potential to evade the adaptive immune response, which often complicates allogeneic cell-based therapies. This review explores recent advancements in inducing pluripotency and utilizing iPS cells to generate differentiated cells. While the ethical and safety concerns surrounding human ES cell use continue, iPS cells may offer a more acceptable compromise. Researchers have made substantial progress in developing safer induction methods and demonstrating that iPS cells can differentiate into various cell types, reversing disease models in mice.

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  Somatic cells can be reprogrammed to a pluripotent state using retroviral transduction of only 4 genes: Sox2, Oct4/Pou5f1, c-Myc, and Klf4. These are termed the “Yamanaka factors”.
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  Non-integrative approaches to iPS induction, such as using adenoviruses or repeated transfections with plasmid vectors, have been attempted to address safety concerns regarding virus-mediated transgene integration.
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  The HDAC inhibitor valproic acid (VPA) significantly improves reprogramming efficiency and allows for efficient reprogramming with only two Yamanaka factors: Oct4 and Sox2. This is significant as VPA is already FDA approved.