State of the Art in Stem Cell Research: Human Embryonic Stem Cells, Induced Pluripotent Stem Cells, and Transdifferentiation

Stem cells divide by asymmetric division and display different degrees of potency, or ability to differentiate into various specialized cell types. Owing to their unique regenerative capacity, stem cells have generated great enthusiasm worldwide and represent an invaluable tool with unprecedented potential for biomedical research and therapeutic applications. Stem cells play a central role in the understanding of molecular mechanisms regulating tissue development and regeneration in normal and pathological conditions and open large possibilities for the discovery of innovative pharmaceuticals to treat the most devastating diseases of our time. Not least, their intrinsic characteristics allow the engineering of functional tissues for replacement therapies that promise to revolutionize the medical practice in the near future. In this paper, the authors present the characteristics of pluripotent stem cells and new developments of transdifferentiation technologies and explore some of the biomedical applications that this emerging technology is expected to empower. 1. Introduction Stem cells represent the building blocks of our bodies, functioning as the natural units of embryonic generation during development, and adult regeneration following tissue damage [1]. They are defined by two distinct characteristics: the ability to maintain themselves through cell division, sometimes after long periods of inactivity (self-renewal), and the ability to give rise to more specialized cell types (differentiation) [2]. Based on the stage in development they are derived from, stem cells are broadly classified as embryonic, umbilical cord, and adult stem cells. Potency of stem cells decreases during development from totipotent stem cells at the morula stage, capable of differentiating into all embryonic and extraembryonic tissues, to pluripotent stem cells at the blastocyst stage, forming all embryonic tissues, and to multi- or uni-potent adult stem cells, forming tissues within their germ layer (Figure 1). Figure 1: Human pluripotent stem cells and their biomedical applications. hESCs are isolated from early embryos obtained by in vitro fertilization or nuclear transfer, and give rise to more specialized cells (pink arrows). Alternatively, reprogramming technologies allow generation of hIPS from differentiated cells, or lineage conversion between differentiated cell types (black arrows). Developmental biology studies are unraveling the characteristics of cell types found at different stages. Stem cells and their differentiated progeny are used in a variety of biomedical