Despite affecting roughly half of the reproductive-age population, menstruation is a topic that comes with a lot of stigma. Talking about periodos can feel embarrassing or uncomfortable for many people, and periods admittedly come with a level of mess and discomfort that can make them a little hard to celebrate. But new, ongoing research investigating the unique properties of stem cells found in menstrual blood might just give todo el mundo cause to celebrate periods. That’s right. Month after month, your body is churning out stem cells that may very well represent the future of medicine, especially for women with endometriosis.
What are stem cells?
Most of the cells in your body are what we call differentiated cells, like how your skin is made up of skin cells. Stem cells, on the other hand, are undifferentiated and able to replicate (multiply) faster and more times than normal cells. Once upon a time, when you were a microscopic blastocyst (just before becoming an embryo)—with cells numbering in the dozens rather than the trillions you would eventually form—todos of your cells were pluripotent stem cells. At that point, they had the potential to become all the cells needed in the human body.
As an adult, you still have stem cells, but these cells are only multipotent because they can only turn into certain types of cells. The most studied and well-known adult stem cells are bone marrow stem cells, and these stem cells can produce different types of blood cells.
A more recent development in stem cell research is induced pluripotent stem cells, in which multipotent stem cells are reprogrammed to mimic embryonic stem cells (but without the cuestiones éticas). This can allow scientists to produce types of cells they ordinarily wouldn’t be able to with adult stem cells. However, according to the Clínica Mayo, this technology is still inefficient, and the scientists can’t always produce the exact type of cell they want.
What are menstrual blood-derived stem cells (MenSCs)?
Adult stem cells work to replace cells as needed within whatever tissue they reside. However, there is one special type of tissue in the body that doesn’t just need to be maintained over time. Instead, month after month, it must become thicker, stimulate new blood vessel growth, and its cells must undergo a morphological transformation. Did you guess? It’s the endometrio, the lining of the uterus.
En un 2022 artículo de la revista Biomedicinas, which outlined the remarkable characteristics of menstrual blood-derived blood cells (“MenSCs”), the authors note that the replacing power of the endometrium comes from the unique stem cells that create it [1]. Namely, MenSCs can replicate twice as fast as bone marrow stem cells, and different kinds of stem cells can be found in the endometrium, meaning MenSCs have the potential to differentiate into many different types of cells. What kinds of cells, you might wonder? Remarkably, these potential differentiations include cells for fat, bone, heart, nerve, respiratory, ovary, liver, pancreatic tissue, and more.
MenSCs also interact with different immune cells, can help moderate the immune system, and seem to play a role in reducing inflammation [1]. Much of this incredible potential has yet to be explored in further studies, but one of the best parts of using stem cells from menstrual blood is that it’s ridiculously easy to get. I mentioned that bone marrow stem cells are currently the best-studied adult stem cell, but bone marrow has to be collected quirúrgicamente, usually from the inside of the hip. Menstrual blood-derived stem cells, on the other hand, are regularly dumped in the trash or flushed away!
The big potential for diagnosing and treating endometriosis with MenSCs
Although it is a common disorder, women with endometriosis have a notoriously difficult time receiving an accurate diagnosis. Pelvic exams and ultrasounds may not detect endometriosis lesions. And while painful periods are a common experience when it comes to endometriosis, otros síntomas like GI problems, nerve pain, fatigue, pelvic pain, and spotting may be overlooked or mistaken for other diseases.
We know that endometriosis is characterized by endometrial-like tissue invading tissue within (and, in some cases outside of) the pelvis. But it’s still unclear why this happens, and why endometriosis lesions act differently than healthy endometrial cells, and why they impact other parts of the body.
MenSCs in women with endometriosis vs. MenSCs in women without endo
However, the aforementioned article on menstrual blood stem cells also describes how MenSCs from women with endometriosis are diferente from MenSCs from women without endometriosis. In women with endometriosis, these stem cells have a different shape, grow differently when incubated, and have different surface markers, all of which could be used to diagnose endometriosis early. Someday, instead of having to undergo pelvic surgery, diagnosis could be as simple as presenting your doctor with a full copa menstrual and having your period blood sent to be examined by a pathologist.
Researchers also found that the endometrial stem cells in women with endometriosis could replicate more frequently, were more invasive, survived longer, and expressed genes related to inflammation and recruitment of more blood vessels to sustain the rogue tissue. These characteristics are remarkably similar to those of cancer cells and help explain why endometrial lesions are so different from normal endometrial tissue.
Researchers also found that the endometrial stem cells in women with endometriosis could replicate more frequently, were more invasive, survived longer, and expressed genes related to inflammation and recruitment of more blood vessels to sustain the rogue tissue. These characteristics are remarkably similar to those of cancer cells and help explain why endometrial lesions are so different from normal endometrial tissue.
Stem cells as a treatment for endometriosis?
Other research on stem cells has furthered our understanding of the role they play in endometriosis. For example, a 2014 study with mice demonstrated that endometriosis lesions could be treated with medicine that inhibited the mechanism by which the lesions recruit more stem cells [2]. Furthermore, a 2023 animal study involving adipose (fat cell)-derived stem cells demonstrated that treating mice with healthy stem cells inhibited endometriosis lesions and improved pregnancy outcomes [3]. While more research is needed, there is hope that one day, normal MenSCs could be used to compete with the abnormal MenSCs that sustain endometrial lesions. This would represent a targeted, non-surgical, therapy for endometriosis.
Besides endometriosis, what else might MenSCs help treat?
The cells in your body derive from three original germ layers: ectoderm, mesoderm, and endoderm. The ectoderm gives rise to skin and nerve cells, the endoderm mainly creates the digestive system, and the mesoderm yields everything else. Adult stem cells can differentiate into other cells in their same germ layer, and stem cells from los tres germ layers have been identified in the endometrium.
This means that there is a huge potential for MenSCs to treat disorders, restore normal function, or heal damaged tissue in many different organ systems. Although there is still a need for human studies, animal models have shown that MenSCs can help with various issues, as outlined by Chen, et. al including [4]:
- Improved beta cell production to treat diabetes tipo 1 in mice [5]
- Improved behavioral outcome following accidente cerebrovascular in rat models [6]
- Improved blood flow in limbs with mice with damaged blood vessels [7]
- Improved fertility following premature ovarian failure mouse models [8]
- Restored function following infarto de miocardio rat models [9]
- Improved liver function in liver disease mouse models [10]
- Improved memory in Alzheimer-like mice [11]
- Improved lung healing in acute lung injury mouse models [12]
- Improved wound closure in mice compared to control groups [13]
Have MenSCs been studied in humans?
What about human studies? A small Estudio de 2016 from China involved using MenSCs to treat seven women with severe Asherman’s syndrome, in which the endometrium is damaged and forms adhesions that contribute to infertility. The patients experienced improved endometrium thickness and one patient in the study achieved pregnancy naturally, with two others conceiving through IVF [14]. Although this was a very small, non-randomized study, the positive results will hopefully warrant further investigation.
What we still have to learn about menstrual blood-derived stem cells
A 2019 overview of MenSCs in Stem Cell Research & Therapy highlighted a few conditions that will need to be met before treatment with these promising stem cells is ready for clinical applications [4]. For one, researchers still need to identify how long transplanted MenSCs can last, and what long-term effects there could be on someone receiving this treatment.
Another issue the article cited is that there has been a wide range of methods used in collecting and studying these cells. Researchers need to determine what the “gold standard” for collection would look like. Furthermore, while early studies have shown that MenSCs have effects on a variety of tissue types, the exact way they interact with different tissues has yet to be further researched and understood [4].
The bottom line on the potential of menstrual blood-derived stem cells: Our bodies are amazing!
While we already knew that the endometrium, or lining of the womb, is a remarkable tissue for how it prepares the female body to welcome and nurture a new life in pregnancy, research now indicates that this power may extend to healing and restoring life in other ways, too. And, since women who take hormonal birth control continuously (as advocated by those who say it’s safe to detener la menstruación indefinitely’) don’t have periods or even the withdrawal bleeds that they would typically experience during their week of placebo pills, menstrual blood-derived stem cells may help usher in a future in which there are even more reasons to ditch birth control and embrace normal cycling. Hopefully, more research into menstrual blood-derived stem cells (MenSCs) will bring about a wave of targeted therapies for a wide range of diseases… all from the simple and renewable resource of period blood.
Referencias:
[1] Cordeiro MR, Carvalhos CA, Figueiredo-Dias M. The Emerging Role of Menstrual-Blood-Derived Stem Cells in Endometriosis. Biomedicines. 2022 Dec 24;11(1):39. doi: 10.3390/biomedicines11010039. PMID: 36672546; PMCID: PMC9856091. [2] Yang J, Huang F. Stem cell and endometriosis: new knowledge may be producing novel therapies. Int J Clin Exp Med. 2014 Nov 15;7(11):3853-8. PMID: 25550893; PMCID: PMC4276151. [3] Huang SJ, Huang C-Y, Huang Y-H, et al. (2023) A novel therapeutic approach for endometriosis using adipose-derived stem cell-derived conditioned medium- A new hope for endometriotic patients in improving fertility. Front. Endocrinol. 14:1158527. doi: 10.3389/fendo.2023.1158527 [4] Chen, L., Qu, J. & Xiang, C. The multi-functional roles of menstrual blood-derived stem cells in regenerative medicine. Stem Cell Res Ther 10, 1 (2019). https://doi.org/10.1186/s13287-018-1105-9 [5] Wu, X., Luo, Y., Pan, R., et. al. Transplantation of Human Menstrual Blood Progenitor Cells Improves Hyperglycemia by Promoting Endogenous Progenitor Differentiation in Type 1 Diabetic Mice. Stem Cells and Development 23, 11 (2014). doi: 10.1089/scd.2013.0390 [6] Borlongan, C., Kaneko, Y., Maki, M., et al. Menstrual Blood Cells Display Stem Cell–Like Phenotypic Markers and Exert Neuroprotection Following Transplantation in Experimental Stroke. Stem Cells and Development. 19, 4 (2009). 10.1089/scd.2009.0340 [7] Murphy, M.P., Wang, H., Patel, A.N. et al. Allogeneic endometrial regenerative cells: An “Off the shelf solution” for critical limb ischemia?. J Transl Med 6, 45 (2008). https://doi.org/10.1186/1479-5876-6-45Referencias, Cont.
[8] Lai, D., Wang, F., Yao, X. et al. Human endometrial mesenchymal stem cells restore ovarian function through improving the renewal of germline stem cells in a mouse model of premature ovarian failure. J Transl Med 13, 155 (2015). https://doi.org/10.1186/s12967-015-0516-y [9] Naoko Hida, Nobuhiro Nishiyama, Shunichiro Miyoshi, et al. Novel Cardiac Precursor-Like Cells from Human Menstrual Blood-Derived Mesenchymal Cells, Stem Cells, Volume 26, Issue 7, July 2008, Pages 1695–1704, https://doi.org/10.1634/stemcells.2007-0826 [10] Lijun Chen, Chunfeng Zhang, Lu Chen, et al. Human Menstrual Blood-Derived Stem Cells Ameliorate Liver Fibrosis in Mice by Targeting Hepatic Stellate Cells via Paracrine Mediators, Stem Cells Translational Medicine, Volume 6, Issue 1, January 2017, Pages 272–284, https://doi.org/10.5966/sctm.2015-0265 [11] Zhao Y, Chen X, Wu Y, Wang Y, et al. (2018) Transplantation of Human Menstrual Blood-Derived Mesenchymal Stem Cells Alleviates Alzheimer’s Disease-Like Pathology in APP/PS1 Transgenic Mice. Front. Mol. Neurosci. 11:140. doi: 10.3389/fnmol.2018.00140 [12] Xiang, B., Chen, L., Wang, X., et al. (2017). Transplantation of Menstrual Blood-Derived Mesenchymal Stem Cells Promotes the Repair of LPS-Induced Acute Lung Injury. International Journal of Molecular Sciences, 18(4), 689. https://doi.org/10.3390/ijms18040689 [13] Cuenca J, Le-Gatt A, Castillo V, et al. (2018) The Reparative Abilities of Menstrual Stem Cells Modulate the Wound Matrix Signals and Improve Cutaneous Regeneration. Front. Physiol. 9:464. doi: 10.3389/fphys.2018.00464
[14] Jichun Tan, Pingping Li, Qiushi Wang, et al. Autologous menstrual blood-derived stromal cells transplantation for severe Asherman’s syndrome, Reproducción humana, Volume 31, Issue 12, 1 December 2016, Pages 2723–2729, https://doi.org/10.1093/humrep/dew235
