It has taken just six years since the release of his seminal publication on the genetic reprogramming of human somatic cells for Shinya Yamanaka to be awarded the most prestigious of all accolades: the Nobel Prize. Compare that to his co-recipient, Sir John B. Gurdon, whose critical paper was first published 50 years ago in 1962 (co-incidentally the year Yamanaka was born), and you begin to appreciate the monumental significance of this development.
In August 2006, Kazutoshi Takahashi and Shinya Yamanaka published a paper that launched them into the stratospheres of scientific reverence. They had, through painstaking trial and error, identified four key factors capable of reverting any cell in the body back to an embryonic-like state. These cells, termed iPSCs (induced pluripotent stem cells), have the capacity to develop into any cell type, and the implications were huge. Stem cell research was a booming field, but ethical issues restricted study of what were the most potent and arguably the most promising cell type: embryonic stem cells. IPS cells gave researchers access to pluripotent stem cells without the controversy, enabling scientists to study disease progression and development in a way that was never before possible. Screening technologies, personalized therapeutics, drug discovery vehicles – it seemed the list of potential applications for these cells were endless. So, six years later, where are we?
Research in the field has come in leaps and bounds. Numerous alternative methods now exist for creating the cells, offering greater safety and more than a 100-fold increase in efficiency compared to the original process. Disease models now exist for indications where there was previously no easily accessible means of study, and Yamanaka recently stated that he would begin supplying clinical grade iPSCs, derived using a technique that entails six transcription factors instead of the conventional four, to encourage therapeutic research in the field. Next year, for the first time, an iPSC-derived therapy will commence phase I clinical trials for age-related macular degeneration (more information here).
However, not all developments have been as expected. It was originally thought that iPSCs would overcome the problem of immune rejection (as, in theory, any patient could generate their own supply of any cell type), but Zhao et al. found that these cells, unlike embryonic stem cells, have a memory of their previous cell type, and are ultimately recognized by the immune system as foreign and rejected. An obstacle to overcome, but with each year that passes our understanding of this extraordinary cell type is becoming more and more refined.
Growth has been exponential. The progression from Gurdon’s frogs to Yamanaka’s cells took 50 years, yet in the six years following we’ve seen iPS cells progress from a theoretical lab experiment to a potential therapeutic. A rate of growth that is impressive by any measure and, personally, I can’t wait to see what it’s going to look like in the next 50 years.
Natasha Davie
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