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A challenge in stem cell research and clinical application is the imbalance between demand and the limited availability of these stem cells. This shortage complicates the development of effective therapies and restricts treatment options for patients. Because stem cells come from unique sources, such as the bone marrow, kidneys, heart and liver, obtaining sufficient quantities can be difficult. Furthermore, ethical concerns regarding sourcing, particularly with embryonic stem cells, make the issue more complex.

Adult stem cells were long suspected to exist in the endometrium. Caroline Gargett’s discovery, almost two decades ago, confirmed this hypothesis. Three different types of stem cells were later identified: epithelial stem cells, mesenchymal stem cells (MSCs) and endothelial stem cells. MSCs, in particular, express CD146 and CD140b/PDGFR-β, which helps in their self-renewing abilities, clonogenicity, plastic adherence and multipotent differentiation. They were noticed in both the functionalis and basalis layer and, every month, while the basalis remains and is regenerated courtesy of the stem cells, the functionalis is shed during menstruation. This led to the investigation of these stem cells in the menstrual fluid and, in 2007, Meng et al. discovered MSCs being shed in the menstrual blood – menstrual blood-derived stem cells (MenSC). He first observed the stem cells in the endometrium and noted their regenerative capacity, amongst other MSC markers, then went on to isolate them.

Comparative advantages

Compared to other sources of MSCs, MenSCs are much preferred because of the regular and periodic non-invasive way they can be collected from menstrual blood. They also do not form teratomas and can be cultured for at least 20 passages without developing genetic abnormalities.

Multipotency and differentiation potential

MenSCs are also remarkable for their broad differentiation capacity. Using specific differentiation techniques, they can be induced to develop into various cell types, including endothelial cells, cardiomyocytes, neurons, cartilage, muscle cells, respiratory epithelial cells, as well as cells from the pancreas, liver, fat tissue and bone. This versatility is achieved through specific differentiation techniques, making MenSCs a valuable resource in regenerative medicine and tissue engineering.

Other biological properties

Immunomodulatory effects

MenSCs’ ability to modulate immune responses make them more suitable for allogeneic transplantation due to the reduced risk of rejection. They prevent inflammatory response by inhibiting T-lymphocyte proliferation, eliciting greater immunomodulatory effects than other MSCs.

Isolation and cultivation

Isolation of MenSC from the menstrual fluid involves easy collection during menstruation and density-gradient centrifugation. Obtained viable MenSCs can then be cultured up to 68 generations with no karyotype alteration, making them a high-yield source.

Applications of MenSC

As a result, numerous studies are concentrating on utilizing MSCs as a promising source of stem cells for regenerative medicine and immunomodulatory therapies in various conditions, including infertility.

Including chemotherapy-induced ovarian insufficiency, MenSCs have shown astonishing results by increasing anti-apoptotic properties and regeneration of ovarian cells, preventing ovarian atresia, prompting follicular development and improving damaged ovarian structures, thereby resulting in fertility and conception. Even exosomes and microvesicles directly secreted by these stem cells proffer the same effects as the MenSCs themselves by regulating the ovarian extracellular matrix in primary ovarian insufficiency rat models, improving ovarian atrophy, restoring estrous cyclicity and other hormone levels. After fertility assessment, an upward trend in the number of live births was noted.

Non-gynaecological applications of MenSC

MenSC therapy was successful in the treatment of a patient with COVID-19 in Hangzhou, China. MenSCs were given intravenously at 3000, 2000, and 3000 U on the 11th, 12th and 14th day of admission, respectively. Results were observed over the next three days, respiratory symptoms improved and temperature decreased. The patient’s leucocyte count and inflammatory cytokines, such as IL-6 and IL-10, decreased significantly. On CT examination, patchy consolidations were absorbed in both lungs and the patient was discharged.

In a study involving injecting stem cells into diabetic mice, the procedure was observed to reverse hyperglycemia by stimulating the regeneration of more insulin-producing beta cells in the pancreas. Results showed improving blood sugar levels from MenSCs.

MenSCs have been studied in the treatment of acute liver failure in mouse models. After administration to a mouse model, MenSCs markedly improved liver function, attenuated collagen deposition, and inhibited activated hepatic stellate cells up to two weeks after transplantation.

MenSCs exhibited neuroprotective properties in oxygen glucose deprivation (OGD)-exposed rat neurons co-culture and protected against ischemic cell death. The mechanism of action after ELISA was via secretion of trophic factors – vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and NT-3 in the co-culture media. Secretion of these growth factors by MenSCs attenuated cellular deficits and behavioural impairments commonly seen in ischemic stroke.

MenSCs in the treatment of heart failure

In a rat model of myocardial infarction (MI), the introduction of MenSCs alongside their conditioned medium (CM) has been shown to reduce infarct size and improve key echocardiographic parameters like ejection fraction and fractional shortening. Specifically, treatment with MenSCs and CM resulted in a noticeable enhancement in cardiac function when measured at intervals post-MI, demonstrating the potential of these stem cells to protect myocardial tissue from further damage. They do this by releasing various growth factors and cytokines that promote healing and regeneration in the heart as well as inhibiting pathways associated with inflammation and cell death such as NF-κB, a key regulator of inflammatory responses.

In wound healing, MenSCs exhibited superior clonogenic and migratory potential compared to umbilical cord-derived MSCs. They greatly enhanced wound closure and neovascularization in murine models, with increased expression of key growth factors and cytokines involved in repair processes. Treated wounds displayed a more robust vascular network and higher collagen content, and prominent VEGF expression was also recorded, indicating effective angiogenesis (the formation of new blood vessels).

MenSCs have also demonstrated significant therapeutic potential across various diseases, including liver fibrosis, muscular dystrophy, stroke and glioma, Duchenne muscular dystrophy, MI, Asherman syndrome, Alzheimer’s disease, acute lung injury, cutaneous wound, endometriosis and neurodegenerative diseases.

What to expect as an MenSC donor

Every menstruating individual is a potential donor, with few exceptions including history of vaginal infection, NSAIDs, corticosteroids and oral contraceptive use within the last three months, infections such as human immunodeficiency viruses, hepatitis C virus and hepatitis B virus, autoimmune diseases, diabetes, endometriosis and malignancies. Donors should also be between 18 and 45 years old. This is because these conditions affect the character and viability of the MenSCs.

The collection process is simple. The MenSCs are collected ideally on the second day of a period, which is usually the heaviest flow day, using a menstrual cup. The collected menstrual blood is then stored in a solution that includes phosphate buffered saline, amphotericin B, streptomycin, penicillin, and Ethylenediaminetetraacetic acid. The sample is kept at a temperature of 4°C and must be sent to the lab for processing within 24 hours after collection.

Promising outcomes have been observed in pre-clinical studies of MenSCs across various conditions. A few case studies have been equally successful. However, compared to other stem cell sources, clinical trials on MenSCs have fewer registrations. The field of regenerative medicine would stand to benefit immensely if this relatively new player is brought to the limelight.

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Peace Chukwu

Peace Chukwu is a medical writer and fourth-year medical student at the University of Nigeria. She also serves as the national Editor-in-Chief for SCORA, a magazine published by the Nigerian Medical Students Association. She tweets @Makuopeace.

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