An exciting development has been made, which could revolutionise IVF treatment, as a team of scientists have finally discovered how to create sperm and egg cells in the lab. This means that patients who are currently unable to produce their own eggs or sperm may be able to use genetically identical eggs/sperm in the future by turning stem cells, or even skin cells, into viable eggs/sperm. Although this has been achieved in animals before, it is the first time that scientists have been able to do the same with human cells. Following this breakthrough, scientists are now hopeful that the method could be refined to aid research and treatment in fertility problems and age-related disease.
Background
Stem cells are the ‘factory’ cells of the body, that can turn into any kind of cell; blood, skin, muscle etc. They are primarily found in the bone marrow, and are used to replace cells and repair the body. Scientists have long attempted to take these cells and manipulate them, in order to change them into required cells for medicinal purposes. For example, teams have been seeking to create organs from stem cells that could be used in transplants. Stem cells have also been studied in the field of reproductive medicine, as scientists have looked to them as a possible source for research and treatment in the area of infertility. To this end, researchers have been attempting to take stem cells and turn them into sperm or egg cells. A team of Japanese scientists achieved this with mice in 2009, after they created primordial gamete cells in a dish. Head scientist Mitinori Saitou discovered that although he could not progress past this stage in the petri dish, when they were injected into mouse ovaries and sperm, they developed into mature cells, which resulted in a litter of baby mice. He also managed to obtain mature sperm and eggs from skin cells after reprogramming them to an embryonic state using iPS (induced pluripotent stem) cell technology.
Following this achievement, others tried to use the same techniques to obtain sperm and eggs from human stem and skin cells. This was met with difficulty, as in most studies very few of the stem cells turned into primordial egg/sperm cells, and the cells produced often required the insertion of additional genes. A paper from Newcastle University claimed to have made sperm in 2009, but was soon retracted amid accusations of plagiarism.
The Study
The Cambridge-based team, led by Dr Azim Surani, managed to replicate the first stage of the Japanese study, producing early-stage human sex cells in the lab. These early-stage cells were produced by culturing embryonic stem cells in the lab, carefully monitoring the conditions. They tried different culturing techniques until hitting upon a successful method, which involved adding growth factors to the cells over the course of 5 days. The major barrier in creating these cells was that, while mouse stem cells are ‘naïve’ and will easily turn into other cell types, human stem cells are ‘primed’ and are less adaptable. Once the team had made the human cells ‘naïve’, they were able to turn 25-40% of the cells into early-stage gametes. After refining the technique, the team showed that the same result could be achieved with skin cells. According to researcher Dr Surani, ‘It’s remarkably fast. We can now take any embryonic stem cell line and once we have them in the proper conditions, we can make these primordial cells in five to six days’. When the artificially created cells were compared to cells from aborted foetuses, they were found to have very similar protein markers.
Next steps
The cells that have been cultured are primitive sperm and egg cells, but scientists are confident that these could be further cultured into mature cells suitable for IVF treatment. The next stage in developing human gametes would be to inject the primitive lab-made cells into the ovaries/testes of mice and other animals to see if they can mature into fully-fledged sex cells. An alternative would be to carry out the entire process of gamete creation and implantation in non-human primates. If animal studies proved that these methods were safe and successful, then the process could be completed in humans, and human sex cells injected into human ovaries/testes.
Even if this method proves not to be successful, the study has given vital insight into the process of creating these cells; in particular the importance played by the SOX17 protein. Gaining knowledge of the mechanisms behind creating sex cells is a crucial step forward and will help improve future research.
Implications
If future studies show that this method is successful, it could pave the way for skin cells to be used to create genetically-identical sperm and eggs for patients undergoing fertility treatment. This step could have the potential to revolutionise fertility treatment, and could be used to help older couples, cancer patients and those with low ovarian reserves to conceive.
There is a theoretical possibility that cells from males could be turned egg cells as well as sperm. This could mean that in the future, same-sex couples might be able to have a genetically related child together via a surrogate, although there would be many practical and ethical issues to overcome. The same would be much harder for women, as they do not possess the male Y-chromosome which is essential for producing sperm.
If this method of creating human sex cells works, it will have an impact on the laws surrounding fertility issues. The law as it stands would have to change in order to enable the use of these cells, as it is currently illegal to use artificial cells for treatment.
Once the remaining logistical and legal obstacles are overcome, it may only be a matter of a few years before the collection of eggs/sperm for treatment is as simple as giving a few skin cells to be turned into sperm or eggs in the lab.