Introduction to iPS cells

Induced pluripotent stem cells, or iPS cells, have quite similar characteristics to embryonic stem (ES) cells, such as pluripotency and unlimited self-renewal, yet can be derived from somatic cells without using embryos [1]. “Pluripotency” is defined as the ability to differentiate in response to extrinsic cues into all somatic lineages that comprise the entire body, including the germ line. An unlimited self-renewal capacity allows a large amount of stem cells to be cultured and grown in the laboratory. Such unique cell identities are programmed in the gene-expression patterns and epigenetic modification patterns of ES cells, and are quite different from other somatic cells. However, the somatic cells can be “reprogrammed” to confer ES cell-like pluripotency by introducing a cocktail of genes (so-called reprogramming factors) – typically Oct4, Sox2, Klf4, and c-Myc. Therefore, iPS cells hold great promise not only for basic biological studies of cell-fate decisions, but also for medical applications. In this chapter, we first summarize a number of methodologies developed to derive iPS cells, and later discuss the recent progress and challenges in the clinical application of iPS cells.

Cells of origin

Many different types of somatic cells have been reprogrammed to pluripotency to generate iPS cells (Table 2.1). Fibroblasts were the first cell type to be reprogrammed [2, 3], and are one of the most widely used cell types so far, because of the well-established culture conditions, distinct morphology from ES cells, high susceptibility to retroviral vector transduction, and their innate ability to serve as feeder cells. Some particular cell types, especially somatic stem cells or progenitor cells, express a number of reprogramming factors endogenously, which presumably allows low-level transduction of some exogenous reprogramming factor(s). For example, adult neural stem cells [4] and dermal papilla cells [5] endogenously express Sox2 and c-Myc, which allows iPS cells to be derived using only two reprogramming factors (i.e. Oct4 and Klf4), although the resulting reprogramming efficiency is lower than that obtained for cells reprogrammed using the four factors. Keratinocytes are an attractive cell source because of their higher reprogramming efficiency [6]. However, the cultivation and expansion of keratinocytes is challenging [7]. In the hematopoietic lineage, the differentiation stage of the cells influences the efficiency of their reprogramming. Hematopoietic stem/progenitor cells generate iPS cells better than do terminally differentiated B and T cells [8].