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Researchers report that they have isolated stem cells from the adult mouse testis that exhibit properties similar to embryonic stem (ES) cells and could in the future be used for growing genetically matched therapeutic cells.
Guan K et al. Pluripotency of spermatogonial stem cells from adult mouse testis, Nature advance online publication, 24 March 2006, doi:10.1038/nature04697
Dr Stephen Minger, Stem Cell Biologist, Kings College London, said:
“This is pretty amazing. It is really interesting that pluripotent cells can still be found in the testes. We would need to replicate this in humans, just because it works in mouse doesn’t necessarily mean it will also work in people.”
Professor Christopher Shaw, Institute of Psychiatry, Kings College London, said:
“Adult pluripotent stem cells have been a holy grail for stem cell biologists for many years. It appears some of us, that is those with testes, were sitting on them all this time. One can quibble about some of their evidence but on the whole they present a credible case. The work needs to be repeated in other laboratories, and of course the technique needs to be optimised in man. But, it could be a very important breakthrough in cellular therapy and provide new insights into genetic diseases, at least for men!”
Professor Colin McGuckin is Professor of Regenerative Medicine, University of Newcastle upon Tyne at the Institute of Stem Cell Biology and Regenerative Medicine, said:
“We know that embryonic-like cells can be found from non-embryonic sources, including human cord blood. The prospect of developing new tools from these mouse-derived cells may allow for the advancement of new technologies for the treatment of human disease. The University of Newcastle has developed a number of new techniques in this way and the paper by Guan and colleagues confirms the importance of searching out new sources of stem cells.”
Professor Harry Moore, Centre for Stem Cell Biology, University of Sheffield, said:
“Researchers have taken an adult stem cell (albeit a germ cell) and shown extensive pluripotency by well characterised assays. Whether this is caused by reprogramming or spermatogonial stem cells represent a special case is not clear.
“The authors speculate that if applied to human spermatogonia the technique could circumvent cloning and embryo use. This is a possibility although there are a number of obstacles to be overcome for this to be successful. Transferring the methods from mouse to human cells may not be Straightforward. While mouse EG cells readility proliferate and cell lines can be established, this is not the case for human EG cells. Mouse and human ES cells also show significant differences in the growth factors they use. Also obtaining human testicular tissue also has its own ethical problems.
“Moreover it is unclear whether the route could be used for women as female germ cells in the adult ovary will have entered meiosis and are not capable of proliferation. A recent paper in Cell (Johnson et al., 2005) disputes this and suggests there is germ cell proliferation in adult mice however this hotly disputed.
“Nevertheless the paper offers an intriguing route for future stem cell therapy which might overcome the use of embryos and cloning.”
Prof Chris Higgins, Director, MRC Clinical Sciences Centre, said:
“If this is right it is potentially interesting as it gives an alternative source of cells for stem cell therapy. The problem to my mind is that they have shown that these cells have some of the properties of ES cells but by no means all – so it would be rather premature to claim they are equivalently useful to ES cells. There needs to be further research before we really get excited about it.
“The possibility of using cells from the testes as an alternative to embryonic stem cells for therapy is intriguing. However, much more research is required before the similarities and differences between these testes cells and embryonic stem cells are understood, and before their potential for use in therapy can be properly assessed.”
Dr Raanan Gillon, Emeritus Professor of Medical Ethics, Imperial College London, said:
“This is a welcome development encouraging those who object to the use of human embryonic stem cells to pursue research with human testicular stem cells. However scientists who share a widespread acceptance of the use of human embryonic stem cells will wish to assess the relevance of this finding for humans by comparing the properties of human testicular and human embryonic stem cells.”
Prof Robin Lovell-Badge, Head of Developmental Genetics, MRC National Institute for Medical Research, said:
“This is a very exciting piece of work. The field of Embryonic Stem (ES) cells arose out of work carried out some 40 years ago on a type of testicular tumour that affects both mice and men called a teratocarcinoma. These fascinated scientists because they are composed of tissues of all three germ layers as well as pluripotent stem cells. It was then shown that teratocaricinomas could be derived experimentally by transplanting early embryos into sites such as the testis. This led to the idea that it ought to be possible to derive the stem cells directly from early embryos in culture, without going through a tumour stage (which inevitably led to the cells acquiring abnormalities in their chromosomes). The idea worked and gave us ES cells in 1981. In this latest paper we have come full circle. The authors have isolated spermatogonial stem cells from adult mouse testis, which would normally only give rise to sperm, and show that these can have much greater potential. But, importantly, by growing these in culture conditions defined by work on mouse ES cells, the authors show that they can turn into what they call multipotent adult germline stem cells (maGSCs) that seem to have many of the properties of ES cells, including essentially immortal growth and an ability to give rise to many different cell types.
“In some ways, therefore, this work does not present any big biological surprise, but this does not devalue its potential importance.
“It will be necessary to see if it is possible to derive similar cells from human testis, especially as human ES cells have different growth requirements. But if so, they should indeed be useful as an alternative to ES cells for research, for example into genetic diseases, and ultimately for therapy. They could even be derived directly from the patient to overcome problems of graft rejection, but unfortunately only for males.
“These findings would also overcome barriers for scientists in countries with regulations that restrict work with human ES cells, such as the authors’ own country Germany, allowing them to join in the effort to both study and treat human diseases with pluripotent cells. But apart from avoiding the use of early embryos, it does not make all the ethical issues go away, especially if there is no difference between maGSCs and ES cells. They could equally be used to make animal-human chimaeras or derive eggs and sperm in the lab.”
A Department of Health spokesperson, said:
“The Government is investing £100m in stem cell research over the next two years. This includes research on all types of stem cells – embryonic, umbilical and adult. It is important we look into all types of stem cells to make sure no opportunities for new treatments are missed.”
Dr Wolf Reik, Head of Developmental Genetics Programme, Babraham Institute, said:
“This is clearly an interesting paper. Thus far, ‘pluripotent’ stem cells (those that can develop into various cell types in the body) have been derived from early embryos, and from embryonic or neonatal germ cells, but not from adult germ cells. Nevertheless, the adult testis has a stem cell population called spermatogonia which keep on self-renewing and producing sperm during adult life. This new work shows that one can derive pluripotent cellines from spermatogonia, and that these cells give rise to various celltypes in the body including germ cells. This is an exciting discovery because it gives us new insights into the biology of pluripotency and reprogramming, and because it opens up a potential new route to stem cell therapy without resorting to the use of somatic cell nuclear transfer (cloning), and is therefore ethically far less complex.”
Prof Malcolm Alison, Stem Cell Biologist, Cancer Research UK, said:
“Males no longer redundant: stem cell keeper in need of remuneration! We are all familiar with the ethical baggage that comes with embryonic stem (ES) cells derived from early foetuses. ES-like cells also can also be obtained from primitive sex organs, also obtained from early embryos. Now, however, it turns out that the adult testis contains cells with the same properties as ES cells. The testis produces sperm, each with half the chromosomal content of a normal adult cell, but now a group of scientists in Germany have found that sperm precursor cells, with the full chromosomal content, have exactly the same potential as ES cells to produce all types of body cells needed for the repair and replacement of organs ravaged by disease and old age. These cells had the same molecular signature as ES cells, and when cultured using the methods normally used to grow ES cells, they looked and functioned like normal adult cells, some like brain neurons, others like beating heart cells and yet others like liver cells. This is great news, a simple biopsy procedure gets hold of these cells; who said the male of the species was becoming redundant?”