Harnessing the potential of induced pluripotent stem cells for regenerative medicine

Abstract

The discovery of methods to convert somatic cells into induced pluripotent stem cells (iPSCs) through expression of a small combination of transcription factors has raised the possibility of producing custom-tailored cells for the study and treatment of numerous diseases. Indeed, iPSCs have already been derived from patients suffering from a large variety of disorders. Here we review recent progress that has been made in establishing iPSC-based disease models, discuss associated technical and biological challenges, and highlight possible solutions to overcome these barriers. We believe that a better understanding of the molecular basis of pluripotency, cellular reprogramming and lineage-specific differentiation of iPSCs is necessary for progress in regenerative medicine.

Figure 1

Schematic representation of the potential utility of iPSC technology in regenerative medicine. Introduction of reprogramming factors, such as Oct4, Sox2, Klf4 and c-Myc, into somatic cells of patients (for example, skin cells, keratinocytes or blood cells) gives rise to iPSCs. These patient-specific iPSCs can then be differentiated into a variety of specialized cell types for a potential use in disease modelling (top) or cell therapy (bottom). The concept behind disease modelling is to reproduce a cellular phenotype in cultured iPSC-derived cells as it occurs in the patient. Such a phenotype could be employed to model this disease for mechanistic studies as well as for large-scale drug screening efforts to identify compounds that could be used to treat any patient suffering from the same disease. The idea behind cell therapy is to generate autologous specialized cells from iPSCs for transplantation into individual patients. Shown in purple are the current limitations in using iPSC technology in regenerative medicine.

Figure 2

Xenogeneic rat-mouse chimaera to produce entirely iPSC-derived rat pancreas. The introduction of wild type rat iPSCs into Pdx1-deficient blastocyst-stage mouse embryos resulted in the generation of a chimaeric rat-mouse that harbours a rat iPSC-derived pancreas. This pancreas is expected to be composed entirely of rat iPSC-derived cells as the loss of Pdx1 in mouse embryos results in the complete absence of a developing pancreas.