Adult stem cells, especially human neural stem cells, have been derived from adult somatic tissue and successfully used to model diseases such as fragile X syndrome. However, the number of adult stem cell lines that can be efficiently derived and expanded in culture is severely limited.
Human embryonic stem cells (ESCs) are pluripotent and expandable, but they are derived from pre-implantation embryos. Although human ESCs have been derived from embryos carrying mutations that cause a range of different disorders, only a few diseases can be diagnosed using pre-implantation genetic diagnosis (PGD). In addition, research involving PGD and human ESCs is controversial and is illegal in some countries.
Induced pluripotent stem cells (iPSCs) can be generated from specific patients with known genotypes and observable phenotypes, and they are therefore ideally suited to disease modelling. iPSC-derived cells have been used to model Mendelian disorders, genetically complex diseases and infectious diseases.
Several studies have used genome editing to correct a disease-causing mutation in iPSCs and thereby show a causal relationship with a disease phenotype. More recently, studies have used gene-edited iPSCs to better understand the molecular mechanisms that underlie disease pathogenesis. Future studies could use genome editing as a tool to understand genetically complex disorders.
iPSC-based models are being used to identify new therapeutics, particularly new drug candidates, and to evaluate drug toxicity. Future work could use these models to stratify patients into drug-responsive and non-responsive groups.
A major challenge is to differentiate the required cell type from iPSCs for disease modelling. In addition, differentiated cells tend to be heterogeneous and immature.