For the first time in the world, scientists at the University of British Columbia (UBC) in Canada have 3D printed human testicular cells and found early signs that they are promising to produce sperm. The research team, led by Dr. Ryan Flannigan, an assistant professor of urology at UBC, hopes the technique will one day provide a solution for male infertility patients who currently cannot be treated.

"Infertility affects 15 percent of couples, and male factors account for at least half of those cases." Flannigan says the lab is based at the Vancouver Prostate Center at Vancouver General Hospital. We are 3D printing testicular cells into a special structure that mimics the anatomy of the human body, which we think is the best way to stimulate spermatogenesis." If successful, it could open the door to new fertility treatments for couples who currently have no other options, Flannigan said.

In the human testis, sperm are produced by small tubules called seminiferous tubules. In the most severe form of male infertility, non-obstructive azoospermia (NOA), no sperm is found in the ejaculate because fewer sperm are produced by these tubular structures. While in some cases doctors can use surgery to help NOA patients find extremely rare sperm, Flannigan says it's only half as successful.

"Unfortunately for the other half of patients, they don't have any choice because we can't find sperm for them." Flannigan says these are the patients his team hopes to help. In the latest study, researchers took a biopsy of the testis of a patient with NOA and harvested stem cells from it. The cells were then grown and 3D-printed on a dish to create a hollow tubular structure, similar to the thin seminiferous tubules that produce sperm.

Twelve days after printing, the team found that the cells had not only survived, but had grown into several specialized cells involved in sperm production and showed marked improvement in spermatogonial stem cell maintenance - all early signs of sperm production capacity. The results of the study were recently published in Fertility and Sterility Science.

"The fact that these cells survive and start differentiating is a huge milestone. There is still a long way to go, but it gives our team hope." Flannigan said.

The team is now working on "training" the printed cells to produce sperm. To do this, they expose the cells to different nutrients and growth factors, and fine-tune their structural arrangements to promote cell-to-cell interactions. If they can be made to produce sperm, those sperm could potentially fertilize eggs through IVF, offering couples a new fertility treatment option.

he research project also revealed the genetic and molecular mechanisms that lead to NOA. Flannigan's team has been using a variety of single-cell sequencing techniques to understand the gene expression and characteristics of each cell, and then running computational models on that data to better understand the root causes of the disease and identify new treatment options. The work also required a high degree of collaboration, involving UBC researchers in the fields of computer science, mathematics, and engineering as well as other international collaborations.

"We are learning more and more that infertility can have many different causes and that each case is individual." "With this in mind, we are taking a personalized, precise approach to medicine -- taking cells from patients, trying to understand their unique abnormalities, and then supporting them with 3D printing to overcome these original defects," Flannigan said.