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:

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.
Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.
First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.
Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.
The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.
Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.
New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.
NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.
Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.
In mice, stem cells seem to work in fighting obesity! What about stem cells in humans?
This release aims to summarize the available literature in regard to the effect of Mesenchymal Stem Cells transplantation on obesity and related comorbidities from the animal model.
More Stem Cells News and Stem Cells Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Processing The Pandemic
Between the pandemic and America's reckoning with racism and police brutality, many of us are anxious, angry, and depressed. This hour, TED Fellow and writer Laurel Braitman helps us process it all.
Now Playing: Science for the People

#568 Poker Face Psychology
Anyone who's seen pop culture depictions of poker might think statistics and math is the only way to get ahead. But no, there's psychology too. Author Maria Konnikova took her Ph.D. in psychology to the poker table, and turned out to be good. So good, she went pro in poker, and learned all about her own biases on the way. We're talking about her new book "The Biggest Bluff: How I Learned to Pay Attention, Master Myself, and Win".
Now Playing: Radiolab

Invisible Allies
As scientists have been scrambling to find new and better ways to treat covid-19, they've come across some unexpected allies. Invisible and primordial, these protectors have been with us all along. And they just might help us to better weather this viral storm. To kick things off, we travel through time from a homeless shelter to a military hospital, pondering the pandemic-fighting power of the sun. And then, we dive deep into the periodic table to look at how a simple element might actually be a microbe's biggest foe. This episode was reported by Simon Adler and Molly Webster, and produced by Annie McEwen and Pat Walters. Support Radiolab today at Radiolab.org/donate.