Human-induced pluripotent stem cells as a source of hepatocyte-like cells: new kids on the block

Excerpt

One of the most exciting recent discoveries in the field of biology was the demonstration that both mouse and human somatic cells engineered via epigenetic reprogramming for the expression of combinations of few defined transcription factors (including Oct4, KLF4, Sox2, NANOG, LIN28, and c-Myc) can become pluripotent [1‐3]. These cells closely resemble embryonic stem (ES) cells for their pluripotency and have been defined as induced pluripotent stem (iPS) cells. These cells have rapidly emerged as very promising tools for the achievement of significant advancement in different fields without the controversies and ethical concerns associated with the use of human ES cells [4]. In particular, the possibility to get iPS cells from readily obtainable somatic cells theoretically opened the way to a number of perspectives and practical applications, including (1) to design and test patient-customized (i.e., autologous) cell therapy without the need for immune suppression and (2) to increase our knowledge on mechanisms of inherited diseases with a realistic opportunity, as recently shown for human iPS-derived hepatocytes [5‐7], for modeling inherited metabolic human diseases, understanding disease pathogenesis, and for drug discovery and testing. It should be anticipated, however, that the latter objective (i.e., the use of human iPS cell-derived hepatocytes for drug discovery and testing) can currently be envisaged as the most useful and safe application. Indeed, a number of relevant limitations have progressively emerged in relation to the clinical use of iPS cells and different laboratories have developed strategies in order to at least partially overcome such limitations. …