Stem cell programming advance

3 June 2013

Edinburgh scientists have taken a vital step forward in understanding how cells from skin tissue can be reprogrammed to become stem cells.

New research could pave the way to generate these stem cells efficiently to better understand and develop treatments for diseases such as multiple sclerosis, Parkinson’s disease and muscular degeneration.

The study of how these cells – known as induced pluripotent stem cells (iPSCs) – were reprogrammed has been published in the journal Nature.

Scientists based at the University's MRC Centre for Regenerative Medicine (CRM) and Anne Rowling Clinic found that the process by which iPSCs are created is not simply a reversal of how skin cells are generated in normal human development. Researchers made the discovery by tracking the change of skin cells during the reprogramming process.

skin cells and stem cellsDuring the reprogramming process adult cells, such as fibroblasts (left), are transformed into induced pluripotent stem cells (right).

All cells in the human body originate from stem cells. In the early embryo these stem cells have the capacity to grow into any specialised cell, such as a skin or muscle cell. However, as the embryo develops, the stem cells lose this capacity.

By reprogramming adult cells to behave like these so-called embroynic stem cells, scientists hope to find ways of treating diseases such as MS, in which some cells of the brain and spinal cord need to be repaired or replaced.

Scientists have been able to create stem cells in this way since 2006 but, until now, it has not been clear how adult cells ‘forget’ their specialised roles.

CRM scientsts found that cells appear to take a detour to an intermediate state during reprogramming.

CRM scientsts found that cells appear to take a detour to an intermediate state during reprogramming. Image credit: James O'Malley.

Experts say that current methods of iPSCs production are time consuming and costly. It takes around four weeks to make human stem cells and even then the process does not always work.

Researchers say that their new insight will enable them to streamline the stem cell production process. The finding may also shed light on how to create different cell types – like muscle or brain cells – that can be used to improve our understanding of diseases and treatment.

CRM and Anne Rowling Clinic scientist Dr Keisuke Kaji, who led the study said: “As exciting as this technology is, we still know very little about how cell reprogramming actually works. Using a new technique, we have improved our understanding of the process. Our work marks an exciting step towards ensuring that induced pluripotent stem cells technology will meet its full potential.”

James O'Malley, PhD student at CRM and first author on the paper, added:"We developed new markers to track the cells. This marker system proved a very powerful tool to study reprogramming. I hope that our results can be used by other researchers to further explore how reprogramming works, and help bring the use of iPS cells closer to reality."

The study was funded by the European Research Council, the Medical Research Council, the Anne Rowling Regenerative Neurology Clinic and the Darwin Trust of Edinburgh.

The publication details are: O’Malley J, Skylaki S, Iwabuchi KA, Chantzoura E, Ruetz T, Johnsson A, Tomlinson SR, Linnarsson S and Kaji K. 2013. High resolution analysis with novel cell-surface markers identifies routes to iPS cells. Nature, published online 02 June 2013, doi: 10.1038/nature12243.

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