Sebastian Kaulitzki/Science Photo Library

Is this the first lab-grown human sperm? A French team claiming the achievement has moved a stage closer to convincing sceptics by having the work published in a peer-reviewed journal. But some researchers say the evidence offered still falls short of what’s required to make such a large and historic claim.

Through a 20-year project, the French researchers say they have made human and rat sperm, starting with testicular cells called spermatogonia. Japanese researchers made mouse sperm in 2011, as did Chinese researchers earlier this year, but the French team is the first to claim the step of making human spermatozoa. “It’s the final 20 per cent of the process,” says Philippe Durand of Kallistem, the company in Lyon pursuing the project.


Last year, Kallistem earned a patent for the technique, but this failed to convince sceptics. Now, the work on rat and human sperm has been published in the peer-reviewed scientific journal Biology of Reproduction.

Kallistem says the aim is to help men unable to make sperm because of treatment for childhood cancer, which often destroys spermatogonia. By taking and freezing biopsies containing spermatogonia before boys begin treatment, the technique could make sperm from these cells in the future when they decide to have children.

72-day process

Durand and his colleagues tried to demonstrated the feasibility of the idea by making sperm using testicular tissue from rats young enough to represent the boys who would benefit from the technique. And to achieve the same feat with human cells, Durand took donated tissue from people undergoing hormone therapy that makes testicular tissue regress to a prepubescent state.

The key, says Durand, is a bioreactor in which bundles of seminiferous tubules – the structures in the testes that contain spermatogonia – are packaged into tiny cylinders of a watery gel called chitosan. The gel is porous and allows air to diffuse in and out of cells. “It’s the permeability that counts, allowing the passage of oxygen and carbon dioxide in and out of the cells,” says Durand. The gel also keeps bacteria in check, he says.

After sealing the ends of the cylinders to keep the cells from spilling out, the researchers immerse them in a dish containing a precise blend of nutrients, vitamins, hormones and growth factors that diffuse through to the cells and coax them to mature, a process that takes 72 days. Afterwards, the cylinder is removed, the chitosan dissolved away – and fully grown sperm extracted from the tubules.

Day 50 and the synthetic human sperm is taking shape M-H Perrard CNRS/Kallistem

Durand says the system works because the tubules allow the spermatogonia to be in constant contact with another kind of cell found in the testicles called Sertoli cells, which help to nourish them and encourage them to mature.

Although the research has been welcomed as a step forward, it still fails to convince other researchers. “This study is encouraging, but the cells isolated are not even closely similar to mature or immature sperm, either in the rat or human,” says Jacob Hanna of the Weizmann Institute of Science in Rehovot, Israel, who is part of another team attempting to grow human sperm in the lab. “While I think the study is important, the claim for complete human spermatogenesis outside the body is completely not proven in this study,” he says.

Proof enough?

Hanna says that the study relies on comparing the physical characteristics of the lab-grown sperm with natural healthy sperm, and on confirming activity in certain genes linked with various stages in sperm maturity.

But these comparisons are not enough to demonstrate that the lab-grown cells are fully developed, healthy sperm, says Hanna. He thinks comparisons of DNA and other markers should have been made. To make “unimpeachable claims”, the team would have to prove that the sperm were able to fertilise eggs, which could have been attempted with the synthetic rat sperm.

Durand says that tests to do exactly that are currently under way. He also says that comparing the physical features of the lab-grown and normal sperm was adequate proof.

Whether or not the sperm are genuine, Kallistem is already in preliminary talks about clinical trials with the ANSM, the body that authorises medicines in France. If all goes well and enough money is raised, trials could start within around four years, says Durand.

Journal reference: Biology of Reproduction, DOI: 10.1095/biolreprod.116.142802