Infertility affects one in seven men of reproductive age worldwide. One idea for treating male sterility is spermatogonial stem cell (SSC) therapy. In this approach, sperm stem cells in the testis are transferred to a test tube, cultured and nudged into becoming fully fledged sperm.
However, a key bottleneck has been identifying just the right conditions to get human SSCs to grow in the lab. Researchers at University of California San Diego School of Medicine have now developed a reliable method for culturing cells with the characteristics of human SSCs. Their work is published in Proceedings of the National Academy of Science.
“We think our approach–which is backed up by several techniques, including single-cell RNA-sequencing analysis–is a significant step toward bringing SSC therapy into the clinic,” said senior author Miles Wilkinson, PhD, Distinguished Professor in the Department of Obstetrics, Gynecology and Reproductive Sciences at UC San Diego School of Medicine.
The Wilkinson team used its single-cell RNA sequencing information to purify what it thought might be human SSCs. Using a method called germ-cell transplantation, it showed that the cells it purified were indeed highly enriched in human SSCs. The team then gathered the profile of genes expressed in these human SSCs to make guesses as to the conditions that might best support their growth in the lab. Using more than 30 human testis biopsies, the researchers determined just the right conditions needed to culture immature germ cells with the characteristics of SSCs.
With that approach, the researchers were able to favor the culture of human cells with the molecular characteristics of SSCs for two-to-four weeks. “Next, our main goal is to learn how to maintain and expand human SSCs longer so they might be clinically useful,” Wilkinson said.