World-first Stem Cell Research Could Aid Male Infertility

The experiment was carried out using mice and produced seven babies, six of which lived to adulthood.

The breakthrough, reported today, Monday July 10, in the academic journal Developmental Cell, helps scientists to understand more about how animals produce sperm. This knowledge has potential applications in the treatment of male infertility.

Karim Nayernia (pictured), who has just taken up a post as Professor of Stem Cell Biology at Newcastle University, led the research while in his previous position at Georg-August University in Göttingen, Germany, with Prof. Dr Wolfgang Engel and colleagues from Germany and the UK, including Dr. David Elliott from Newcastle University's Institute of Human Genetics.

Stem cells have the potential to develop into any tissue type in the body and could therefore be used to develop a wide range of medical therapies.

Prof Nayernia, of the Newcastle-Durham-NHS Institute for Stem Cell Biology and Regenerative Medicine*, and his team describe in their paper how they developed a new strategy for generating mature sperm cells in the laboratory using embryonic stem cells from mice. They then went on to test whether this sperm would function in real life.

The team isolated stem cells from a blastocyst, an early-stage embryo that is a cluster of cells only a few days old.

These cells were grown in the laboratory and screened using a special sorting machine. Some had grown into a type of stem cell known as ‘spermatogonial stem cells’, or early-stage sperm cells.

The spermatogonial cells were singled out, then genetically marked and grown in the laboratory. Some of them grew into cells resembling sperm, known as gametes, which were themselves singled out and highlighted using a genetic marker.

The sperm that had been derived from the embryonic stem cells was then injectd into the female mouse eggs and grown into early-stage embryos.

The early-stage embryos were successfully transplanted into the female mice which produced seven babies. Six developed into adult mice.

The work was funded by the University of Göttingen and the Germany Research Council (DFG).

Prof Nayernia, who originally hails from Shiraz in Southern Iran, said: “This research is particularly important in helping us to understand more about spermatogenesis, the biological process in which sperm is produced. We must know this if we are to get to the root of infertility.

“If we know more about how spermatogonial stem cells turn into sperm cells, this knowledge could be translated into treatments for men who are unable to produce mature sperm, although this is several years down the line.

"For example, we could isolate a patient’s spermatagonial cells using a simple testicular biopsy, encourage them in the laboratory into becoming functional sperm and transplant them back into the patient.”

The findings could also inform a field of stem cell research known as nuclear transfer, or therapeutic cloning, which aims to provide tailor-made stem cells to aid disease therapy and infertility. Sperm cells could potentially be created using this method.

Prof Nayernia and his team in Germany were the first in the world to isolate spermatagonial stem cells. The team was also able to show that some of these stem cells, called multipotent adult germline stem cells (maGSCs), turned into heart, muscle, brain and other cells.

Although previous studies have shown that embryonic stem cells grown in the laboratory can become germ cells that give rise to cells resembling sperm cells or gametes, this is the first time scientists have tested whether the gametes really work in real life.

Prof Nayernia added: “Spermatogonial stem cells are extremely promising and more research is needed to establish their full potential.”

* The Institute for Stem Cell Biology and Regenerative Medicine (ISCBRM draws together Durham and Newcastle Universities, the Newcastle upon Tyne Hospitals NHS Foundation Trust and other partners in a unique interdisciplinary collaboration to convert stem cell research and technologies into cost-effective, ethically-robust 21st century health solutions to ameliorate degenerative diseases, the effects of ageing and serious injury. The Institute has received substantial funding and other support from the regional development agency, One NorthEast. See: www.iscbrm.org/

* Stem cell biology and regenerative medicine is one of four major research themes which underpin Newcastle's development as a 'Science City'. The UK Government designated Newcastle a 'Science City' because of its research excellence and potential to contribute to UK's knowledge economy. See: www.ncl.ac.uk/sciencecity/