(Ed: Read Peace’s blog about the promise of menstrual stem cells and then learn how they can be used to treat endometriosis, below.)
Endometriotic lesions. Image freepik.
Endometriosis is a chronic illness that affects 5-15 per cent of the female population. It is a disease in which tissue similar to the lining of the uterus grows outside the uterus. It can cause severe pain in the pelvis, inflammation, infections and make it harder to get pregnant. There is a substantial reduction in the quality of life of symptomatic women. Expression of symptoms mostly ranges from significant to incapacitating and rely on estrogen to develop and grow.
For a long time, the etiology of endometriosis has remained unclear and termed an idiopathic (the cause is unknown) or multifactorial illness of the female reproductive system, with some probable theories like retrograde menstruation, low vitamin D levels, immune system sub performance and genetic susceptibility. However, new research supports that this illness could indeed be caused by retrograde menstruation where migratory cells, specifically migratory menstrual stem cells (MenSCs) move from the uterus through the fallopian tubes and into spaces such as the abdomen, ovaries, lung parenchyma and even the brain, where they develop into endometrial tissue and shed monthly.
The shedded blood becomes trapped in the space and causes inflammation, cysts, scarring and tissue adhesions, conditions all associated with varying degrees of pain. The adhesions involving organ-to-organ or multi-organ binding cause fertility issues in the long run. This theory, first hypothesized by Dr. John Sampson, an endometriosis pioneer and former president of the American Gynaecological Association (1923), also explains the anatomical distribution of superficial endometriosis lesions. He thought they were influenced by clockwise peritoneal currents, which created a pattern with more lesions found in the right side of the peritoneal cavity than the left.
Stem cells for endometriosis
The discovery of stem cells in menstrual blood, plus the retrograde theory, suggests a treatment.
Mesenchymal stem cell programming for endometriosis
MenSCs, originating from mesenchymal stem cells (MSCs), possess significant therapeutic potential, as they can migrate to injury sites, differentiate into various cell lineages, secrete soluble factors, and modulate immune responses, similar to bone marrow MSCs.
MSCs secrete a variety of bioactive molecules that play crucial roles in modulating immune inflammatory responses and promoting lymphocyte differentiation, as well as aiding in the regeneration and remodelling of damaged tissues. Research, using a horse model of endometriosis, has demonstrated that treatment with MSCs leads to decreased expression levels of IL-1β, IL-10, TNF, and IL-1R, while levels of IL-6 and IL-8 increase. This suggests that MSCs exert regulatory effects on inflammatory factors. The reduction of IL-1β and TNF is beneficial for downregulating chronic inflammation, which aids in managing endometriosis and reflects the immune-inflammatory mechanisms through which MSCs contribute to its treatment.
A recent study examined MSCs isolated from both eutopic and ectopic endometrial tissues in patients with endometriosis. The results demonstrated that ectopic MSCs exhibited significantly greater proliferation, migration, and angiogenic (growing new blood vessels) potential compared to their eutopic counterparts, and control MSCs from individuals without endometriosis. Notably, treatment with sorafenib, a tyrosine kinase inhibitor, effectively reversed these enhanced characteristics in ectopic MSCs by reducing their proliferation and motility, as well as inhibiting key signaling pathways involved in angiogenesis, such as vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-alpha (HIF-1α) expression14.
Furthermore, once introduced into the abdominal cavity, these ectopic MSCs can proliferate and differentiate into endometrial cells, leading to the formation of ectopic implants. Since only differentiated endometrial cells express steroid hormone receptors, MSCs may contribute to the persistence and recurrence of endometriosis following hormonal treatments. This suggests that targeting MSCs could enhance treatment efficacy, particularly when combined with existing hormonal therapies. Inhibiting angiogenesis, for instance, presents a promising therapeutic strategy in managing endometriosis as it addresses the underlying stem cell dynamics that sustain ectopic lesions.
Early diagnosis as a result of MenSC analysis
There is a significant delay between the onset of initial symptoms and the diagnosis of endometriosis, with the condition going undiagnosed in two out of 10 cases. Current diagnostic methods primarily involve laparoscopy and biopsy. However, these procedures are invasive, and they often serve not only as diagnostic tools but also as surgical treatment options.
Recent studies show that the MenSCs from women with endometriosis and those without have been discovered to be morphologically, phenotypically and functionally different. Endometriotic MenSCs (E-MenSCs) have far greater capacity for invasion and proliferation, in addition to higher adhesion potential. CD marker patterns showed higher expression of CD9, CD10, and CD29. E-MenSCs co-cultured with allogeneic peripheral blood mono-nuclear cells (PBMCs) show elevated levels of indoleamine 2,3-dioxygenase-1 (IDO1) and cyclooxygenase-2 (COX-2), indicating enhanced immunomodulatory activity. Non-endometriotic (NE)-MenSCs have higher forkhead transcription factor-3 (FOXP3) levels. Additionally, E-MenSCs-PBMC co-cultures yield increased interferon-γ, IL-10, and MCP-1 levels in the supernatant.
As markers for these cells have been identified, research is now geared towards screening endometriosis using these parameters.This means that it is possible to screen women for endometriosis by simply obtaining a sample of their menstrual fluid.
MenSC results in infertility
The structural and functional changes caused by endometriosis to the reproductive system complicates fertility. About 30-50 per cent of women with endometriosis are infertile and 25-50 per cent of women with infertility, about 190 million, have endometriosis according to the World Health Organization.
Following autologous MenSC transplantation, MenSCs can differentiate into endometrial cells and secrete bioactive factors that enhance tissue repair, reduce inflammation and improve endometrial function thereby restoring fertility in women suffering from conditions like intrauterine adhesions. Moreover, the immunomodulatory effects of MenSCs promote a favourable cytokine environment that supports embryo implantation and development. Their ability to enhance vascular remodelling further aids in creating a supportive endometrial environment for pregnancy.
Clinical applications of MenSCs in endometriosis treatment
Owing to the discovery of stem cells in menstrual blood and their involvement via the retrograde flow, exosomes from NE-MenScs have been used in endometriosis to reduce endometriotic lesion formation tendencies. They have the potential to modify and repair E-MenSCs in women with endometriosis.
Exosomes were secreted and isolated from healthy NE-MenSCs via density-gradient centrifugation, characterized by flow cytometry and applied to E-MenSCs. Various cell mechanisms and pathways such as inflammation, proliferation, apoptosis, migration, and angiogenesis were then examined using techniques including Real-Time PCR, ELISA, immunocytochemistry, annexin V/PI assays, and scratch assays. Results recorded a significant reduction in the level of markers related to inflammation, proliferation, migration and angiogenesis in E-MenSCs. Also, further evaluation in both gene and protein levels showed that apoptosis of the endometriotic MenSCs was induced, thanks to the treatment.
Due to its renewable and readily accessible nature, menstrual blood can be regarded as a reliable and cost-effective resource for research focused on the cellular and molecular aspects of endometriosis. Hopefully this will encourage more follow-up studies on patients to fully explore the long-term efficacy and safety.
Peace Chukwu
Latest posts by Peace Chukwu (see all)
- New turn for stem cell therapy: How tiny messengers are about to change the game - June 18, 2025
- Menstrual stem cell implication in endometriosis - February 6, 2025
- Menstrual stem cells and their promise - January 10, 2025
Comments