The concept of “stem cells” first emerged in the 1960s when transplanted mouse marrow-derived cell colonies were shown to have the ability to differentiate into three hematologic lineages: erythrocytes, granulocytes, and megakaryocytes [1]. After this, researchers began searching for the progenitor cells responsible for generating all other cell types during embryonic development. It was not until the early 1980s that mouse embryonic stem cells (mESCs) were first successfully isolated and established as in vitro cultures [2,3]. In the past 3 decades, newer platforms, including human embryonic stem cells (hESCs) [4], human induced pluripotent stem cells (hiPSCs) [5], and, most recently, chemically induced pluripotent stem cells (CiPSCs) [6], have been developed as tools for disease modeling, drug discovery, and regenerative medicine.

Each platform provided a promising glimpse of what the revolutionizing field of stem-cell research had to offer in terms of therapeutics and translational medicine. However, they all share a common set of technical challenges: how to develop a renewable and efficient source of pluripotent cells, maintain a stable population of pluripotent cells in the undifferentiated state without accumulating genetic abnormalities, and guide differentiation to yield a homogenous somatic cell population. In this chapter, we will focus on a discussion of CiPSCs, the most recent technology (reported in July 2013), and their advantages, disadvantages, and application in regenerative medicine [6].

Pluripotent stem cells can be derived through either direct harvesting of embryonic stem cells (ESCs) or, more recently, reprogramming of somatic cells. The latter was first achieved by Yamanaka’s group using a cocktail of four transcription factors (Oct3/4, Sox2, Klf4, and c-Myc) [5, 7], circumventing the ethical dilemma of destroying the fertilized embryos associated with ESCs and providing an autologous source of stem cells less prone to immune rejection after transplant. However, hiPSCs must still overcome several limitations, such as low cellular reprogramming efficiency, incomplete reprogramming resulting in heterogeneous population of cells, and risk of tumorigenesis [8]. In particular, c-Myc and Klf4 are known tumorigenic proteins, whose interactions with p53 lead to genomic instability. Within the last year, one study has reported successful reprogramming of murine somatic cells into CiPSCs using only small molecules [6].