The research team were delighted to find abundant bovine spermatogonial stem cells thriving in the mouse testes, since they are hard to spot in tissue sections. Once the researchers learned to isolate these elusive sperm-producing cells from bull calfs, they transplanted them into mouse testes. Despite the foreign surroundings, the bovine cells survived for long periods, up to three months, although they failed to fully develop into sperm, said de Rooij.
"Our plan is to develop a culture system for spermatogonial stem cells" de Rooij told conference attendees. Although admitting the leap to humans is considerable, the colonised mouse testes are already providing useful insights.
"We'd like to know how to culture human spermatogenic stem cells to restore male fertility after cancer therapy," says Hannu Sariola, from the University of Helsinki in Finland who is also working towards a similar goal.
Bizarrely, a brain cell growth factor also has a powerful influence on spermatogonial stem cells. Glial cell derived neurotrophic factor (GDNF) is also involved in spermatogenesis: levels are high during the neonatal period and drop in adulthood. Indeed, mice that have been genetically manipulated to express high levels of GDNF in the testes produce huge clusters of spermatogonial stem cells. But the risk of cancer is boosted too, so it is not just about turning on the GDNF tap indiscriminately. It must be tightly regulated, Sariola pointed out.
The Dutch researchers are also hunting for the ideal conditions and nutrients that will coax spermatogonial stem cells into becoming sperm. So far, they have found that growth factors GDNF and fibroblast growth factor (FGF) seem to be necessary to enhance cell growth. The team's next move is to transplant monkey and human cells into the mouse testes system.
"It is truly remarkable that mouse testes can sustain these bovine cells in culture," says Elaine Dzierzak, who coordinates a EuroSTELLS project at Erasmus University Medical Centre in Rotterdam. Testicular cultures could also prove an ideal system to test compounds that might affect sperm-production such as endocrine disruptors or therapeutic drugs.