The promise of induced pluripotent stem cells in research and therapy

Abstract

The field of stem-cell biology has been catapulted forward by the startling development of reprogramming technology. The ability to restore pluripotency to somatic cells through the ectopic co-expression of reprogramming factors has created powerful new opportunities for modelling human diseases and offers hope for personalized regenerative cell therapies. While the field is racing ahead, some researchers are pausing to evaluate whether induced pluripotent stem cells are indeed the true equivalents of embryonic stem cells and whether subtle differences between these types of cell might affect their research applications and therapeutic potential.

Figure 1. Morphology of pluripotent stem cell types

Mouse ES (a) and iPS (b) cells form dome-shaped, refractile colonies. These colonies are in contrast to the flat morphology of mouse epiblast-derived stem cells (f), which resemble human ES (d) and iPS (e) cells. Human iPS cells induced into a naive pluripotent state by treatment with chemical inhibitors^– (c) parallel the morphology of mouse ES and iPS cells. Scale bars, 50 μm.

Figure 2. Medical applications of iPS cells

Reprogramming technology and iPS cells have the potential to be used to model and treat human disease. In this example, the patient has a neurodegenerative disorder. Patient-specific iPS cells — in this case derived by ectopic co-expression of transcription factors in cells isolated from a skin biopsy — can be used in one of two pathways. In cases in which the disease-causing mutation is known (for example, familial Parkinson’s disease), gene targeting could be used to repair the DNA sequence (right). The gene-corrected patient-specific iPS cells would then undergo directed differentiation into the affected neuronal subtype (for example, midbrain dopaminergic neurons) and be transplanted into the patient’s brain (to engraft the nigrostriatal axis). Alternatively, directed differentiation of the patient-specific iPS cells into the affected neuronal subtype (left) will allow the patient’s disease to be modelled in vitro, and potential drugs can be screened, aiding in the discovery of novel therapeutic compounds.