Chapter 2 – Pluripotent Stem Cells and Gene Therapy

Over the past decade, our understanding of stem cell biology has rapidly expanded with the discovery that any mammalian somatic cells can be genetically reprogrammed into a pluripotent state with the potential to differentiate into any cell lineage. Induced pluripotent stem cells (iPSCs) have revolutionized current experimental approaches for understanding the pathophysiological underpinnings of diseases with genetic etiologies. While the translational potential of human iPSCs to correct genetic diseases is great, there is yet no consensus on how to maximize human iPSC production while minimizing negative off-target effects, such as tumorigenesis or immunogenicity of transplanted cells. In this chapter, we will summarize the various reprogramming factor requirements and gene delivery methodologies that have been employed in generating human pluripotent stem cells. We will further focus on the clinical translation of human iPSC technology by discussing how it can be used to model disease as a cell-source for drug discovery and as a direct therapy for reversing phenotypes caused by genetic diseases.