Noncell autonomous reprogramming to a pluripotent state

In 2006, Takahashi and Yamanaka discovered that somatic cells could be reprogrammed to a pluripotent state by the expression of a defined set of exogenous transcription factors. This represents a significant breakthrough for the practical use of stem cells in regenerative medicine. Since then, several strategies have been used to generate induced pluripotent (iPS) cells that include nucleic acid and nonnucleic acid-based approaches, with and without epigenetic modifications. The purpose of these different approaches for generating iPS cells, besides understanding the -underlying mechanism, is to develop a facile method for reprogramming without genetic alteration, suitable for clinical use. Here, we discuss different strategies for generating iPS cells, with an emphasis on a recent noncell autonomous approach to reprogram somatic progenitors that regenerate cornea to a pluripotent state through the recruitment of endogenous transcription factors.