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Pluripotent stem cells from strength to strength

It has been ten years since the discovery of induced pluripotent stem cells (iPSCs) by Kazutoshi Takahashi and Shinya Yamanaka. In a Perspectives article published online in Nature Reviews Molecular Cell Biology this week, Takahashi and Yamanaka describe the path that led to the discovery and discuss the current state of iPSC-based therapeutic applications.

Pluripotent stem cells, which are derived either from pre-implanted human embryos or, in the case of iPSCs, from somatic cells (any cell in the body except egg and sperm cells), can potentially be directed to form almost any cell type of the body. Nuclear reprogramming – whereby the nucleus from a differentiated somatic cell is converted to a pluripotent embryonic-like state – was first achieved by nuclear transfer in the 1960s by Sir John Gurdon, who won the Nobel Prize with Yamanaka in 2012. This was followed by the first report of iPSCs in 2006 in mice, and the first report of human iPSCs one year later. Since then, technical advances in how iPSCs are generated and cultured have allowed them to be used in treatment of sickle cell anaemia, Parkinson’s disease and spinal cord injury – all in mouse studies.

Although the mechanisms underlying cellular reprogramming are still poorly understood, it is widely recognized as a powerful technology. The first clinical trials using human iPSCs for treating wet age-related macular degeneration – a condition which leads to loss of vision – are currently underway in Japan, with the aim of assessing the safety and effectiveness of iPSC-based therapies in humans. ‘We now hope that further trials of iPSC-based therapies, accompanied by basic research focused on gaining more detailed, molecular insights into the process of molecular reprogramming itself, will result in unveiling the full potential of iPSCs in the next decade,’ write the authors.

Several articles about pluripotent stem cells – from their molecular characteristics to their use in the clinic – are published in this month’s Focus issue of Nature Reviews Molecular Cell Biology, commissioned to mark the 10-year anniversary of the discovery of iPSCs.