Stem Cell Therapy May Restore Fertility After Ovarian Failure
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Stem cell therapy could be used to restore fertility and healthy hormone levels after ovarian failure – due to a genetic condition or following chemotherapy – according to results from a preclinical study in mice. The research was conducted by a team from Brigham and Women’s Hospital and published in eBioMedicine.
Rates of ovarian failure set to rise
Premature ovarian failure impacts approximately five percent of people with ovaries, stemming from either cancer treatment or genetic issues. “Some of these patients [with premature ovarian insufficiency] are as young as 17 years old. Additionally, a significant number of patients over the years have been reproductive-age women who have breast cancer and ovarian failure from chemotherapy,” says Dr. Raymond Manohar Anchandirector of the stem cell biology and regenerative medicine research laboratory at Brigham.
With cancer rates among young adults on the rise, the number of people experiencing infertility as a result of chemotherapy is also expected to increase. Yet, there are currently no therapies available to restore fertility after chemotherapy. Instead, people with ovarian failure rely on freezing their own eggs or embryos prior to treatment or using donor eggs in order to have children. Unfortunately, the referral rates for egg or embryo freezing before cancer therapy are low.
As well as impacting fertility, ovarian failure is associated with other health issues – such as loss of bone mass and poor heart health – due to falling hormone levels. Hormone replacement therapy is a treatment option, but limited data on the potential health consequences associated with its long-term use has driven calls for therapies that preserve or restore ovarian function.
Could stem cell therapy be the answer?
The new study used cells from mouse ovaries – called granulosa cells – to create induced pluripotent stem cells (iPSCs), which can differentiate into any cell type. In the lab, the granulosa-derived iPSCs preferentially differentiate into ovarian cells, perhaps due to their epigenetic memory. The researchers illustrated that these ovarian cells could produce physiological concentrations of the reproductive hormones estrogen and progesterone, and were also able to differentiate into egg cells.
The mice receiving the stem cell therapy were also able to naturally conceive and birth live mouse pups that also went on to birth another generation of mice.
“This proof-of-principle study shows that you can take non-reproductive cells and make them into functional eggs that can develop into multiple generations of live animals,” Anchan says.
The most exciting finding, according to Anchan, was that treatment of one ovary with the stem cell therapy induced egg and hormone production in the other ovary: "The stem cells must be secreting a factor promoting this healing process. We're now looking at what the factor or factors might be. Identifying such a factor or factors would be doubly exciting because perhaps we can treat some patients with this factor without having to inject any cells."
This research shows promise for revolutionizing fertility treatments for people with ovarian failure, but further studies are needed to prove that it can be translated from mice into humans. The researchers are also currently investigating the long-term health of the offspring of the mice that received the cell therapy. “Treatment safety is paramount,” explains Anchan, “it is very important to analyze the pups and stem cell-derived eggs for normal genetics.”
The research could also advance our understanding of how gametes develop and potentially be used to establish a platform for in vitro egg maturation for use during in vitro fertilization.
“If this research is translatable into humans, we would open up a whole new therapeutic avenue for patients to have biological children,” concludes Anchan.
Reference: Elias KM, Ng NW, Dam KU, et al. Fertility restoration in mice with chemotherapy-induced ovarian failure using differentiated iPSCs. eBioMedicine. 2023. doi: 10.1016/j.ebiom.2023.104715