New method '100-fold' better at stem cell reprogramming

A novel and more efficient method of generating iPS (induced pluripotent stem) cells from adult cells using small RNA molecules has been discovered by researchers at the University of Pennsylvania School of Medicine in the USA.

Prior to the study, reprogramming adult cells into stem cells involved the use of four key transcription factor genes. The technique, pioneered by Professor Shinya Yamanaka in 2006, was relatively inefficient with fewer than 20 cells successfully reprogrammed per 100,000 adult cells. Using the microRNA-mediated method, however, the new study reports that approximately 10,000 of the adult cells were reprogrammed per 100,000.

MicroRNAs are short RNA molecules that bind to complementary sequences on messenger RNA and block expression of a gene. The team discovered the new approach through their work on microRNAs in lung development, in particular a cluster called miR302/367.

This same cluster of microRNAs had been shown to be highly expressed in stem cells and to change the appearance of cells. When the investigators expressed the microRNAs in mouse 'fibroblasts' - common cells also found in human skin - they observed colonies that looked just like iPS cells.

'We were very surprised that this worked the very first time we did the experiment', said senior author Professor Edward Morrisey, scientific director at the Penn Institute for Regenerative Medicine: 'We were also surprised that it worked much more efficiently than the transcription factor approach pioneered by Dr Yamanaka'.

The mechanism for the method remains unclear. Since microRNAs block gene expression, it may be they repress the repressors of the four transcription factors and other factors important for maintaining pluripotency.

Professor Morrisey believes the work is a 'game changer', saying: 'This is the first time we've been able to make induced pluripotent stem cells without the four transcription factors and increase the efficiency by 100-fold… We think this method will be very valuable in generating iPS cells from patient samples in a high-throughput manner'.

'Generating iPS cells efficiently is paramount for their potential therapeutic use', said Dr James Kiley, director of the National Heart, Lung, and Blood Institute's Division of Lung Diseases. 'This novel study is an important step forward in that direction and it will also advance research on stem cell biology in general'.

The team and several collaborators are now trying to direct these iPS cells to develop into heart, liver and other tissue cells. The study was published in the journal Cell Stem Cell.