Induced pluripotent stem cells: progress towards a biomedical application

Some 5 years ago, Takahashi and Yamanaka first obtained induced pluripotent stem cells (iPSCs) by genetically 'reprogramming' adult somatic cells (fibroblasts). This breakthrough opened a new frontier in regenerative medicine, in which iPSCs might effectively replace embryonic stem cells (ESCs), with the additional advantage of permitting autologous transplant. Unfortunately, the risk of aberrant reprogramming and of the complications related to the use of transgenes in the process still hinders iPSC clinical application. Nevertheless, differentiation of iPSCs derived from patients may already provide a formidable platform for the in vitro analysis of human disease mechanisms and their modulation by drugs. Such an approach has already been validated by the finding that iPSCs obtained from patients with a specific genetic syndrome can be differentiated into cardiomyocytes retaining the gene abnormality and recapitulating, at the cell level, the syndrome functional phenotype. Unlike the use of iPSCs in regenerative therapy, their development as disease models is unencumbered by safety constraints. Whatever the intended use, the availability of reliable and reproducible methods for somatic cell reprogramming, iPSC expansion and differentiation is pivotal and remains a major challenge to date. The article by Burridge and coworkers describes a process encompassing all the phases in the preparation of precursor-derived cardiomyocytes, characterized by unprecedented efficiency and, most notably, applicable to different human precursors, including ESCs and iPSCs derived from multiple somatic cell types. Provided that the process will prove reproducible when applied by different laboratories, the contribution of Burridge and coworkers may represent a genuine leap in the development of precursor-derived technologies.