Weekly Comment

No embryo required: human stem cells from the skin

By Mike Nagle

- Last updated on GMT

A startling breakthrough has allowed scientists to create human
stem cells from just reprogrammed skin cells, with no embryo and
thus, perhaps no ethical dilemma.

In fact, two sets of scientists have independently taken the leap forward. One group in the US and another in Japan used a retrovirus to carry four genes to the fibroblast cells, converting them to pluripotent cells "that exhibit the essential characteristics of embryonic stem cells,"​ according to James Thomson and his colleagues at University of Wisconsin-Madison - one of the teams to crack the problem. The ability to generate embryonic stem cells without using an embryo will negate much of the ethical debate that has dogged the field over the years. Coupled with the fact that these cells are much easier to generate and the end result is likely to be more scientists using stem cells both to screen new drugs and eventually, as the therapy themselves. "It's going to completely change the field,"​ said Thomson. His group, including lead researcher Junying Yu have published their results in the online edition of the journal Science​. A further advance is that the cells can be created from a patient's own skin cells, ensuring that they are not rejected by the immune system. Back in 1998, Prof. Thomson was the first to extract stem cells from fertilised human embryos. Since then, scientists have been battling to find an easier and more ethical way of collecting the cells. One method is somatic cell nuclear transfer (SCNT), where the nucleus of an unfertilised embryo is removed and then replaced with a nucleus from another cell, often fibroblasts. The embryo reprogrammes the fibroblast nucleus and, once shocked, it begins to divide like a fertilised embryo and is the first step to cloning animals, including the infamous Dolly the sheep. The same process has also been used to harvest stem cells and although the technique also side-steps immune system rejection, it still involves embryos. Since the development of SCNT, scientists have reasoned that if they could find out what proteins inside the embryo transformed the fibroblast nucleus, they might be able to use those proteins on their own to transform an intact skin cell into a stem cell - and without the need for an embryo. The Japanese group who have succeeded in doing just this is headed by Shinya Yamanaka at Kyoto University. In June 2005, they accomplished it in mice and since then have been toiling to repeat their success using human cells. The results of their success have been published in the journal Cell​. Although the techniques pioneered by Thomson and Yamanaka are essentially the same, there are some crucial differences. Both teams used the OCT3/4 and SOX2 genes but whereas Yamanaka then added KLF4 and c-MYC to the mix, Thomson used NANOG and LIN28. This confers one definite advantage to Thomson's technique because the rival method involves the oncogene c-MYC. However, Yamanaka used adult human cells, whereas Thomson's group created the stem cells from foetal fibroblasts, or postnatal foreskin fibroblasts. The two methods also differ in terms of efficiency: Yamanaka's technique reprogrammed one in 5,000 cells; Thomson's was better for foetal cells - one in around 4,500 - but less successful for postnatal cells where the efficiency was about one in 10,000. Although the development is undoubtedly exciting, Thomson notes that more study of the newly-made cells is required to ensure that the "cells do not differ from embryonic stem cells in a clinically significant or unexpected way, so it is hardly time to discontinue embryonic stem cell research."​ The Wisconsin Alumni Research Foundation, which holds controversial patents on embryonic stem cells, has said it has applied to patent Thomson's latest research. The next step in the research is to find a way of achieving the same thing but without the final cells being contaminated by the viruses used to carry the genes. This increases the likelihood of genetic mutations in the cells and therefore, them causing cancer. The viral vectors could be removed after the process but, an even better solution would be to find molecules that can switch the genes back on in skin cells. Until either solution is found, it is too early to think about using the cells as a therapy, although they can start to be used in drug screening experiments. Both teams say that traditionally derived embryonic stem cell research should be continued. "We are still a long way from finding cures or therapies from stem cells and we don't know what processes will be effective,"​ Yamanaka said. However, that hasn't stopped UK scientist Prof. Ian Wilmut, the man behind Dolly the sheep, from announcing to British newspaper The Daily Telegraph that he plans to abandon SCNT in favour of these new techniques.

Related topics: Preclinical Research

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