A startup out of Utah, Paterna Biosciences, says it has successfully grown functional human sperm in a lab and used the sperm to make visibly healthy-looking embryos. The technique could eventually help men with certain types of infertility have biological children.
The findings have not yet been published in a peer-reviewed journal or independently verified. WIRED is the first to report the advance.
The process involves isolating sperm-making stem cells from testicular tissue and coaxing the cells into becoming fully-fledged sperm in a dish. Scientists have been attempting to produce sperm outside the body, known as in vitro spermatogenesis, for almost a century. A Japanese team was the first to produce viable mouse sperm in the lab in 2011, but making human sperm has turned out to be a more difficult task.
Another biotech company, Kallistem in France, claimed it achieved in vitro spermatogenesis in 2015, but some outside researchers questioned whether the sperm were fully developed, and the company did not prove that the sperm were able to fertilize eggs.
It takes a little over two months and several steps for sperm-forming stem cells to become mature sperm in the body. After stem cells are produced in the tightly coiled tubules of the testicles, they undergo meiosis, dividing to create cells with 23 chromosomes. This is when sperm also develop the tail and head structure needed for swimming. From there, sperm move to another part of the testicles, where they gain the ability to swim. A tube called the vas deferens then transports the sperm and releases them into the ejaculate.
“There are very strict control mechanisms at every single one of those steps,” says Alexander Pastuszak, CEO and cofounder of Paterna, who is also a board-certified urologist and an associate professor of surgery at the University of Utah School of Medicine. “We’ve figured out the instructions that are needed to teach these stem cells to become mature, normal sperm.”
Paterna initially tested whether the testicular tubules in which sperm mature could be cultured in the lab and used to derive sperm but found that wasn’t the best approach. Ultimately, the company found a way to nurture just the sperm-forming stem cells in a dish and coax them into becoming sperm. The team used computational biology to predict the molecular signals that are important at every step of the sperm-making process. They then tested various combinations of molecules to induce each of those stages until settling on the right cocktail.
“This is huge,” says Larry Lipshultz, a professor of urology at Baylor College of Medicine, who is not involved with Paterna. “People didn't understand, or had never figured out, what growth factors you have to supply to these cells to get them to become mature sperm. Apparently, they've identified these substances.”
Being able to generate sperm in the lab has long been a goal for the fertility field. Roughly half of all infertility cases are linked to male factors, which include low sperm count, abnormal sperm shape, or poorly swimming sperm. About 10 to 15 percent of infertile men have a complete absence of sperm in the ejaculate and have few to no options for having biological children. This is the group Paterna is initially hoping to help. While they don’t produce sperm, these men still seem to have the stem cells that give rise to sperm, Pastuszak says.
Research by Paterna and others suggests that it’s not that the stem cells that are faulty, but that the surrounding microenvironment, which includes support cells, is somehow defective. By mimicking a healthy environment in the lab, Pastuszak thinks the company can produce healthy sperm.
The goal, he says, is to create thousands of sperm from a standard tissue biopsy. The company has had a high success rate in generating sperm from dozens of tissue samples.
Pastuszak says early testing shows the lab-made sperm look “effectively identical” to naturally made sperm. The procedure is not yet ready to be used to start pregnancies, though. Paterna created embryos as an early test to validate that its lab-made sperm was actually viable. The company plans to conduct a larger, more comprehensive study involving men with infertility. Paterna will extract sperm from their ejaculate or testicular tissue and use its method to generate sperm for the men. From there, the company will use both the extracted sperm and lab-made sperm to fertilize eggs in the lab, compare fertilization rates between the two groups, and analyze the resulting embryos for physical and genetic abnormalities.
“That will actually tell us a ton regarding the efficacy and safety of the approach. It will tell us if there are any mutations that are created by the in vitro process,” Pastuszak says. After that, trials of lab-made sperm to start pregnancies could begin as soon as next year.
Certain types of medication, intrauterine insemination, and conventional in vitro fertilization, or IVF, can help men with reduced sperm quantity or quality. But for men who make no sperm at all, treatment options are more limited.
“In terms of male infertility, the most challenging scenarios for clinicians are where men don’t have any sperm,” says Ryan Flannigan, a surgeon who specializes in sperm retrieval at the Vancouver Prostate Centre in Canada, who is not part of Paterna. “You see the emotional toll and the impact on these individuals and couples.”
For these men, a surgical procedure that looks for sperm in testicular tissue is an option. It requires general anesthesia and can take as long as four hours, depending on how quickly sperm are found. Even then, surgeons fail to find sperm in a significant percentage of cases.
Paterna's technology is designed to replace that process, instead taking a small biopsy of testicular tissue in a doctor’s office. That tissue would be sent to Paterna, which would perform in vitro spermatogenesis. The company plans to charge somewhere between $5,000 and $12,000 for the procedure.
Flannigan says Paterna’s technique could also be used for boys who undergo chemotherapy for cancer treatment before puberty, since sperm-forming stem cells are present from birth. Young cancer patients have had the option of freezing and preserving testicular tissue for years, but transplanting it back remains experimental, and no births have been reported.
Other efforts to produce sperm in the lab are focusing on induced pluripotent stems, skin or blood cells that have been reprogrammed to an embryonic-like state. These stem cells can be coaxed into any type of cell in the body using the right set of instructions. Scientists have successfully produced functional sperm and eggs from mouse pluripotent stem cells and created healthy offspring. The technique, known as in vitro gametogenesis, could be used to help same-sex couples have biological children, since an egg or sperm could hypothetically be created from a skin sample.
Justin Dubin, a urologist and director of men’s sexual health at Baptist Health Miami Cancer Institute, says Paterna’s advance is exciting but cost will be a limiting factor for many patients in the US and other places where fertility treatments are prohibitively expensive.
“We’re coming up with so many amazing options in fertility care, and yet so many of them are not covered by insurance,” he says.
“It’s a huge disservice to our patients, to the world’s population, by not providing people with the means to achieve the family that they want.”
