Sperm derived from stem cells – Experts reaction

Scientists in China have created functioning sperm from mice stem cells in the laboratory.

Flickr/Umberto SalvagninTo accomplish this feat, the researchers coaxed mouse embryonic stem cells to turn into functional sperm-like cells, which were then injected into egg cells to produce fertile mouse offspring.

The research, published in Cell Stem Cell, provides a platform for generating sperm cells that could one day be used to treat male infertility in humans, say the authors.

You can read more about the research on Scimex.org.

A University of Otago study published last year found that male infertility problems are “common” among Kiwi men; by the age of 38, around 22 percent of men report some fertility difficulties.

The SMC gathered the following expert commentary.

Prof Gareth Jones, Bioethics Centre and Department of Anatomy and Structural Biology, University of Otago, comments:

“For the moment, this scientific breakthrough will hold out hope for many with infertility problems, on the proviso that it translates seamlessly to human beings.

“There are at least two major underlying ethical considerations.

“The first is the derivation of the sperm cells from embryonic stem cells involving the destruction of embryos. This is inherent within any use of embryonic stem cells and not specifically for the production of sperm cells.

“If future developments are able to bypass the use of embryos, by starting from induced pluripotential stem cells, derived from mature tissue, this objection could largely disappear.

“The second ethical consideration looks ahead to a time when both sperm cells and eggs may be able to be derived in this way. This would set the scene for producing embryos entirely from artificially derived germinal cells. In this way it would prove possible, theoretically anyway, to use artificially produced embryos as the starting point of new individuals.  We will have to see whether this would prove as revolutionary as it sounds. But there is little doubt it will be seen as contentious.”

Comments collected by the UK Science Media Centre:

Prof Allan Pacey, Professor of Andrology, University of Sheffield, comments:

“This is an interesting study which represents a further step forward in our abilities to produce sperm outside the body in a laboratory dish. This would be a remarkable thing to be able to do, both for the advancement of science and also to be able to help infertile men father children that are genetically theirs. But no-one has managed to do this yet.

“One of the major concerns about lab-made sperm is whether or not they are genetically the same as healthy sperm produced in the body. Therefore it’s reassuring to see that the scientists in this study have paid very careful attention to this and their results appear to show that the sperm-like cells they have made are genetically normal.

“However, it’s important to note that the sperm-like cells produced in the study were not fully mature sperm as we might know them. They appear to be early sperm cells called spermatids.

“These contain the same genetic material that fully formed sperm do, but they do not have the ability to swim as the sperm tail is not yet formed properly. So in order to fertilise they must be injected into an egg in the same way that an embryologist does when performing ICSI as part of IVF.

“Therefore, in spite of these encouraging results, we are still some way from immediately applying this technique as a potential cure for human male infertility.

“Moreover, in their experiments the authors used embryonic stem cells as their starting material. But to make sperm for infertile men, it would probably be necessary to use an adult cell from some part of their body.

“Therefore, it remains to be seen if this technique could be applied in humans to create sperm-like cells that might be useable in IVF. That needs further work and I hope someone already has this underway.”

Prof Daniel Brison, Professor of Clinical Embryology and Stem Cell Biology, University of Manchester, comments:

“This is a very exciting study showing the feasibility of producing functional male gametes in the laboratory.  There are many technical obstacles before this technology could be applied to men, and the major issue is safety.

“There are already concerns that children produced by conventional assisted reproduction technologies using sperm produced normally in the body may be at risk of altered health outcomes (see New Scientist this week).  Therefore before laboratory-made sperm could be used to produce children, extensive safety testing would have to be carried out.  Nevertheless this appears to be a major scientific advance in meiosis research.”

Prof Simon Fishel, Founder & President, CARE Fertility Group, comments:

“This is exciting research that may represent a possible avenue in the longer term for male infertility. However, establishing safety along with reproducibility will be key before it can be considered as an option for clinical practice, but one can only encourage an acceleration of further important studies in this area, whilst congratulating the authors on their work to date.

“We do have therapies today for most male factor conditions offering men the chance of their own genetic child. However in those few conditions when we cannot acquire sperm cells to inject into the egg – such as failure in the manufacturing process – this remains an intractable problem for men wanting their own genetic child.

“This study was done using mice and with embryonic stem cells; it remains to be understood how embryonic stem cells could be used to aid the above mentioned clinical conditions. But it does open up prospects for further research.”

Comments from GENeS (Genetic Expert News Service) in the US:

Dr Terry Hassold, Professor, School of Molecular Biosciences, Washington State University, comments:

“This has been the black box of these kind of studies: no one has been able to push cells through meiosis and get a functional gamete out of the other end. Most of us who work in the field think that it is too complicated. Importantly, these results need to be replicated in another laboratory, but there’s no question this is a significant advance if they have taken a cell that is not a germ cell and have got progeny out of the other end.

“The crucial test is whether or not this technique does reliably give rise to genetically normal progeny. The authors do a little bit of work which suggests the progeny are genetically and epigenetically balanced, but there now has to be much more careful characterization, particularly with respect to what’s going on with meiosis – are they getting the right number of chromosomes, and is the chromosome content normal? The bottom line is that this is meiosis lite.

“There’s no question that the technique needs to be improved further, but if we can build on this as a technique that is doable in the laboratory, it really is going to change the way we think about cases of infertility that are currently unable to be treated by IVF.

“The crucial question is whether someone else going to be able to replicate the study, and if that is the case then it really will revolutionize assisted reproduction as we know it. All the IVF clinics would be likely to hop on it, although in my opinion that would be very premature.”

Dr Vittorio Sebastiano, Assistant Professor, Department of Obstetrics and Gynecology, Stanford School of Medicine, comments:

“This study is certainly a milestone in the field. While in vitro derivation of germ cells capable of meiosis had already been proven to some extent, the work of this group surpasses previous attempts, especially considering that the cells were capable of giving rise to viable embryos that could develop into mouse pups. This “functional” test represents the gold standard and until now no-one had been able to show this using an in vitro-only approach.

“The application of this technique to human cells may not, however, be as easy. So far only two groups have shown to be able to generate germ-like cells from human pluripotent cells but there’s no definitive evidence that those cells can progress and mature further. The gene expression profile of human germ cells is similar but still different from that of mouse germ cells. In principle the technique could work in human cells but it may require a few more years to achieve similar results

“The technique described in this paper could potentially be adapted as an infertility treatment if induced pluripotent stem cells (iPSCs) could be generated from infertile men, differentiated into germ cells and further matured by combining them with cells derived from testicular biopsies. Although this approach is not in principle different from being able to generate any other “dysfunctional” organ from patient-derived iPSCs, the fact that we are not simply restoring the functionality but potentially creating cells that could be used to generate embryos raises an endless number of ethical questions and concerns that we have not yet fully discussed.

“The reason is very simple: whatever alteration we may cause during the process of reprogramming or differentiation of the cells will be passed on to the following generations, and we cannot predict how this could impact the life of the babies that would be conceived using this technique. It is a fascinating topic of discussion.”