The number of ovarian follicles decreases with age and can't regenerate naturally. Stem cells can potentially restore damaged tissues due to their ability to change into different cell types.
This post will cover stem cells and how they could potentially help restore ovarian function, especially in patients with a poor response to ovarian stimulation or with premature ovarian insufficiency (POI).
What Are Stem Cells?
Stem cells are unique cells in the body that can develop into different cell types, like muscle cells or brain cells. They serve as a repair system for the body, replacing damaged cells and tissues. Stem cells can do two important things: they can make copies of themselves through self−renewal and differentiate or transform into specific types of cells. This dual ability allows stem cells to replenish dying cells and regenerate damaged tissues throughout a person's life.
Stem cells are essential for tissue regeneration and are consequently distributed throughout the body. The diagram below highlights various locations where stem cells are found and the types of cells they can differentiate into.
Modified from Cacciottola et al. 2023, CC BY 4.0
Stem cells are rare within tissues but play a crucial role in repairing tissues by differentiating into the necessary cell types; they differentiate into different cell types by responding to signals around them, like growth factors or cytokines. For example, when skin is damaged, various signals can activate stem cells to become skin cells to help heal the injury.
How Can Stem Cells Rejuvenate the Ovaries?
When stem cells are injected into the ovary and tracked, they don't appear to enter the follicle − Cacciottola et al. 2023. It tells us they probably aren't differentiating into egg or follicular cells. So, can stem cells benefit the ovary? They may be secreting factors that improve the health of the follicle. Stem cells might be secreting beneficial factors, like growth factors, either alone or bundled together with other factors in special compartments called exosomes.
Exosomes are tiny vesicles, or small bubbles, released by cells. Exosomes are a way for cells to communicate with other cells and are filled with biological materials such as proteins, lipids, DNA, and RNA. Exosomes act as carriers for these materials and can influence the behavior of surrounding cells to promote cell survival or tissue repair.
Modified from Kalamedits, CC BY−SA 4.0, via Wikimedia Commons
These exosomes secreted by stem cells may provide beneficial factors to the follicle to promote ovarian rejuvenation.
What Is the Evidence for Stem Cells in Ovarian Rejuvenation?
There have been additional studies investigating the use of stem cells in ovarian rejuvenation, reviewed by Cacciottola et al. 2023.
Animal Studies
Much of the research is based on animal models that have been subjected to chemotherapies or other toxins to simulate ovarian damage or in aged animals to simulate the decline in ovarian function with advancing age. Stem cells from different sources have also been investigated.
Studies in animal models have shown that stem cells can decrease apoptosis (cell death) and regulate the main processes within the ovarian environment. Studies have also shown that stem cells can improve blood vessel formation, reduce inflammation, and potentially even have anti−aging effects on the ovary. It has resulted in follicle count increase in animals, improved hormone functions, and better reproductive outcomes like higher pregnancy rates and healthier egg development.
Human Studies
Aside from animal studies, human studies have also been done. In women who respond poorly to ovarian stimulation or for those with POI, stem cells have been proposed as a way to help protect the existing follicles and improve outcomes:
- After injecting ovaries with bone marrow−derived stem cells, Herraiz et al. (2018) showed an improvement in ovarian function in 81.3% of women with poor ovarian response, with increases in antral follicle counts (AFC) and antimüllerian hormone (AMH) levels. There were five pregnancies in this study.
- Preliminary results from an ongoing clinical trial by Pellicer De Castellvi et al. (2020)found improved AFC after bone marrow−derived stem cell injection in women with POI and menses recovery in 40% of women. This study reported one ongoing pregnancy (at 20 weeks).
- Mashayekhi et al. (2021) showed that 4 of 9 POI patients had recovered menses after adipose−derived stem cell injection. There were no differences in AFC or AMH levels.
- Yan et al. (2020) found improved ovarian function in umbilical cord−derived stem cell injections POI patients, with increased follicular development and more eggs retrieved. There were four live births in this study, with standard development.
While these results are promising, Cacciottola et al. 2023 noted that all these studies have shown a live birth rate of about 10% in patients with POI who were treated with stem cells, which is comparable to spontaneous pregnancy rates in these patients (with temporary ovarian reactivation).
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Conclusions
Stem cell therapy could help rejuvenate ovaries in IVF treatments, especially for women with poor ovarian response or premature ovarian insufficiency (POI). This therapy works because stem cells can turn into different types of cells and release helpful substances like growth factors and cytokines. These substances can make ovarian follicles healthier, which might improve fertility.
Much of the evidence supporting stem cell therapy for ovarian rejuvenation comes from animal studies, which show promising results such as decreased cell death, improved blood vessel formation, and enhanced ovarian function. Human studies have also been conducted, providing preliminary data that stem cell injections can improve ovarian function in women with POI or poor ovarian response, resulting in some successful pregnancies and live births.
