Nav: Home

Researchers restore fertility in non-human primate model of childhood cancer survivorship

March 21, 2019

PITTSBURGH, March 21, 2019 - One in three childhood cancer survivors is at risk of becoming infertile due to chemotherapy or radiation, and since their sperm or eggs have not matured, assisted reproduction using those sperm or eggs is not an option when they become adults. Now in a major first, researchers at the University of Pittsburgh School of Medicine and the Magee-Womens Research Institute (MWRI) have reported in a non-human primate model that immature testicular tissue can be cryopreserved, and later used to restore fertility to the same animal.

The advance, reported in Science, marks a milestone in the development of next generation assisted reproduction therapies, and offers hope for fertility preservation in prepubertal boys who are about to undergo cancer treatments.

"We grew up in families ourselves, and I imagine that many of us dreamed about growing up and having our own families," said the study's senior author Kyle Orwig, Ph.D., professor of obstetrics, gynecology and reproductive sciences at Pitt's School of Medicine and an MWRI investigator. "This advance is an important step toward offering young cancer patients around the world a chance at having a family in the future."

Boys are not born with mature sperm. Rather, hormonal changes during puberty lead to an increase in testosterone, which activates stem cells in the testes to start producing sperm. In prepubertal boys, chemotherapy, radiation or other medical treatments can kill these stem cells and cause permanent infertility.

"Previous research in non-human primates has demonstrated that sperm could be produced from autologous transplants of frozen prepubertal testicular tissue, but the ability to produce a healthy live offspring - the gold standard of any reproductive technology - has not been achieved until now," said first author Adetunji Fayomi, Ph.D., a former graduate student in Orwig's lab and postdoctoral scholar at Pitt.

In the current study, Orwig and his team developed a non-human primate model of cancer survivorship. Prior to treating with chemotherapy, the researchers cryopreserved immature testicular tissue. They later thawed and transplanted pieces of the tissue under the skin of the same animal.

Eight to 12 months later, after the animals entered puberty, the researchers removed the grafts and found large numbers of sperm to be present. They sent the sperm to their collaborators at the Oregon National Primate Research Center at Oregon Health and Science University who were able to generate viable embryos, which were then transferred to recipient females.

In April 2018, one of the females gave birth to a healthy female baby, which Orwig named "Grady" - a portmanteau of "graft-derived" and "baby."

"With Grady's birth, we were able to show proof-of-principle that we can cryopreserve prepubertal testicular tissue, and later use it to restore fertility as an adult," Fayomi said.

The authors note that in comparison to previous work, they used a different cryopreservation protocol and grafted larger pieces of testicular tissue, which may have contributed to the success of the current effort.

In preparation for clinical translation, Orwig established a fertility preservation program in 2010 at UPMC Magee-Womens Hospital. The program offers pediatric cancer patients the option of cryopreserving testicular or ovarian tissue before starting cancer treatments. Since then, it has expanded through collaborations with centers around the world. Orwig hopes that when these patients grow up and want families of their own, they'll have that option.

"The reason that we did these studies in a non-human primate is because we thought that this was really the last step on the road to translating to the clinic," Orwig said. "Having produced a live-born and healthy baby, we feel that this is a technology that is ready to be tested in the clinic."
-end-
Additional authors on the study include Karen Peters, B.S., Meena Sukhwani, Ph.D., and Hanna Valli-Pulaski, Ph.D., all of Pitt; Gunapala Shetty, Ph.D., and Marvin L. Meistrich, Ph.D., of The University of Texas MD Anderson Cancer Center; Nicola Robertson, M.S., Victoria Roberts, Ph.D., Cathy Ramsey, B.S., Lisa Houser, B.S., Carol Hanna, Ph.D., and Jon D. Hennebold, Ph.D., all of Oregon National Primate Research Center at Oregon Health and Science University; and Ina Dobrinski, D.V.M., Ph.D., of the University of Calgary.

The study was funded by National Institutes of Health grants P01HD075795, R01 HD076412, HD076412, P51OD011092 and the Magee-Womens Research Institute and Foundation.

To read this release online or share it, visit http://www.upmc.com/media/news/032119-orwig-fertility-science [when embargo lifts].

About the University of Pittsburgh School of Medicine

As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support.

Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see http://www.medschool.pitt.edu.

About Magee-Womens Research Institute

Magee-Womens Research Institute (MWRI) is the largest research institute in the U.S. devoted exclusively to health conditions affecting women and infants. The Institute is leading discoveries and advancing knowledge in the field of reproductive biology and medicine, translating this knowledge into improved health, wellness and disease prevention for women, engaging our community in women's health, and training the present and future generations of women's health researchers.

http://www.upmc.com/media

Contact: Erin Hare
Office: 412-864-7194
Mobile: 412-738-1097
E-mail: HareE@upmc.edu

Contact: Arvind Suresh
Office: 412-647-9966
Mobile: 412-509-8207
E-mail: SureshA2@upmc.edu

University of Pittsburgh

Related Stem Cells Articles:

A protein that stem cells require could be a target in killing breast cancer cells
Researchers have identified a protein that must be present in order for mammary stem cells to perform their normal functions.
Approaching a decades-old goal: Making blood stem cells from patients' own cells
Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body.
New research finds novel method for generating airway cells from stem cells
Researchers have developed a new approach for growing and studying cells they hope one day will lead to curing lung diseases such as cystic fibrosis through 'personalized medicine.'
Mature heart muscle cells created in the laboratory from stem cells
Generating mature and viable heart muscle cells from human or other animal stem cells has proven difficult for biologists.
Mutations in bone cells can drive leukemia in neighboring stem cells
DNA mutations in bone cells that support blood development can drive leukemia formation in nearby blood stem cells.
Scientists take aging cardiac stem cells out of semiretirement to improve stem cell therapy
With age, the chromosomes of our cardiac stem cells compress as they move into a state of safe, semiretirement.
Purest yet liver-like cells generated from induced pluripotent stem cells
A team of researchers from the Medical University of South Carolina and elsewhere has found a better way to purify liver cells made from induced pluripotent stem cells.
Stem cell scientists discover genetic switch to increase supply of stem cells from cord blood
International stem cell scientists, co-led in Canada by Dr. John Dick and in the Netherlands by Dr.
Stem cells from diabetic patients coaxed to become insulin-secreting cells
Signaling a potential new approach to treating diabetes, researchers at Washington University School of Medicine in St.

Related Stem Cells Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Climate Crisis
There's no greater threat to humanity than climate change. What can we do to stop the worst consequences? This hour, TED speakers explore how we can save our planet and whether we can do it in time. Guests include climate activist Greta Thunberg, chemical engineer Jennifer Wilcox, research scientist Sean Davis, food innovator Bruce Friedrich, and psychologist Per Espen Stoknes.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...