Ovarian decline and premature ovarian insufficiency are life-changing conditions for many women, often leading to infertility and reduced hormonal health. These conditions, often caused by genetic issues, immune system problems, or environmental factors such as chemotherapy, are difficult to diagnose and treat. Against this backdrop, researchers have reviewed the evidence for a treatment that combines two different types of stem cells: mesenchymal stem cells and hematopoietic stem cells. This combined therapy could offer new possibilities for repairing ovaries and improving women’s health.

Professor Aleksandar Ljubić and his team wrote this review; the team spans Pronatal Hospital in Belgrade, the Academy of Sciences and Arts of Bosnia and Herzegovina, Medigroup Health System, the University Clinical Center of Serbia, and the University of Belgrade. Their review is published in the International Journal of Molecular Sciences. Professor Ljubić’s team explains that the two cell types in this “dual-double” stem cell therapy can be given at the same time, known as dual, or one after the other, known as double.

The strength of the therapy comes from the way the two cell types work together. Mesenchymal stem cells, which are stem cells that can turn into bone, fat, or cartilage cells and can be taken from bone marrow, fat tissue, or umbilical cord, are known for reducing inflammation and helping new blood vessels grow. Hematopoietic stem cells, which are the cells that form blood and immune cells and are usually taken from bone marrow or blood, play an important role in repairing the immune system and supporting cell growth. When used together, they are thought to create a healthier environment for the ovaries to recover. Professor Ljubić noted that “the combined infusion of bone marrow-derived mesenchymal stem cells and hematopoietic stem cells could enhance ovarian function, increase follicle numbers, and restore hormonal balance in women with premature ovarian insufficiency”.

Early results from small studies are encouraging. In one study in which women with premature ovarian insufficiency received stem cells taken from their own bone marrow, half of them started having menstrual cycles again, and one in four became pregnant naturally. In other studies, roughly 30 to 40 percent of treated women resumed menstrual cycles. In some cases, hormone levels important for fertility, such as estrogen, improved noticeably. Professor Ljubić stressed that “notably, several patients achieved successful pregnancies following the treatment, highlighting the regenerative potential of this combined therapy”.

Scientists have proposed several ways in which the therapy may work. Mesenchymal stem cells and hematopoietic stem cells release helpful natural substances such as vascular endothelial growth factor, a protein that stimulates blood vessel growth, and hepatocyte growth factor, a protein that supports cell repair. These substances improve blood supply and protect ovarian cells from damage. In animal studies and early clinical reports, this has been linked to healthier egg development, better hormone balance, and improved ovarian reserve, which is the body’s ability to produce eggs. The treatment may also help women whose ovaries were damaged by chemotherapy during cancer treatment.

At the same time, researchers stress the importance of caution. Growing mesenchymal stem cells in the laboratory before using them can, in some cases, lead to tumor formation. Treatments involving hematopoietic stem cells can sometimes cause side effects such as infections or slow recovery of the immune system. These risks highlight the need for strong safety checks, careful patient follow-up, and well-structured clinical protocols before the treatment can be offered widely.

In conclusion, dual-double stem cell therapy represents a promising step forward in reproductive and regenerative medicine. By combining the repairing ability of mesenchymal stem cells with the immune support of hematopoietic stem cells, the therapy could provide a well-rounded path to restoring ovarian health. While more studies and strict safety measures are still needed, the findings suggest that in the future women facing premature ovarian decline could have access to a treatment that helps restore ovarian function and fertility.

Journal Reference

Ljubić A., Dinić M., Švraka D., Vujović S. “Dual-Double Stem Cell Ovarian Therapy: A Comprehensive Approach in Regenerative Medicine.” International Journal of Molecular Sciences. 2025; 26(1): 69. DOI: https://doi.org/10.3390/ijms26010069