A potential role for insulin-like growth factor signaling in induction of pluripotent stem cell formation

Recent success in reprogramming somatic cells into induced pluripotent stem cells (iPS cells) with a cluster of nuclear transcription factors, such as Oct4, Sox2, Klf4, and c-myc, opens up a new era in regenerative medicine. However, reportedly poor efficiency and slow kinetics of the reprogramming process by viral transfection of the nuclear factors may create an obstacle that hampers clinical application of the iPS cell technology. Furthermore, the viral transfection may induce mutagenesis and raises the risk for cancer development. Hence, generation of iPS cells using a non-viral approach appears to be an important prerequisite for iPS cell-based regenerative medicine. Through its receptor/phosphoinositide 3-kinase (PI3-K) signaling pathway, insulin-like growth factor (IGF) plays a critical role in promotion of survival and proliferation in a diversity of cell types, including both embryonic and adult stem cells. In addition, IGF may enhance expression of reprogramming or surviving factors in reprogramming somatic cells. This review summarizes recent advances in IGF research and discusses the potential for IGF to act as a co-stimulatory factor for somatic cell reprogramming and iPS cell development. Currently available evidence from experimental animal and human studies highly suggests that IGF may contribute to reprogramming of somatic cells into iPS cell generation, and enhancement of iPS cell survival and growth, which will be instrumental in regenerative medicine.