Stem Cells Obtained From Menstrual Blood May Epigenetically Inhibit Liver Cancer

Menstruation is a normal and natural part of human life. In most cases, it signifies a healthy reproductive system and a women’s ability to bear children.  For far too long, however, it has been viewed in a negative light and not always appreciated for its real purpose, which is preparing the female body for pregnancy.

Hopefully, science will finally change the overall perspective on menstruation as newer reports are confirming that menstrual blood and tissue are valuable resources of mesenchymal stem cells (MSCs). These stem cells, meant to aid the developing fetus, could potentially be used to regenerate human tissue, fight disease, and even target microscopic tumors. Most notably, these stem cells are readily available and can be isolated non-invasively from voluntary female donors without invoking ethical concern.

In a recent study, researchers tested menstrual derived MSCs (MenSCs) on a certain type of liver cancer to determine if they could conceivably inhibit tumor cell growth. The results revealed that these stem cells indeed induced an anticancer effect, which was observed for the first time to occur via specific epigenetic alterations. Their findings were reported in the May issue of Stem Cell Research & Therapy.

The role of epigenetics in the initiation and development of cancer has been broadly explored over the years. In particular, changes in DNA methylation, or the addition of a 5-carbon on cytosine residue (5mC), has been implicated in several studies from breast cancer to brain cancer and more. Although many of these analyses are highly correlative, they do underscore the prospective connection between epigenetic pathways and disease.

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Malignant tumor progression is highly dependent upon microenvironmental composition. Since epigenetic mechanisms act as an interface between the environment and a cell’s genome, changes made to these mechanisms can indicate a disruption in the normal cellular functions. As well, they point out important crosstalk between cancer cells and their neighboring microenvironment components.

Cancer cells are dynamic and can reshape their epigenomes in response to alteration in their surroundings. However, they are also capable of reprogramming the tumor microenvironment toward an immunosuppressive state, thus limited the body’s defense mechanisms to eradicate the tumor cells.

MSCs are one of the main types of cells situated in the tumor microenvironment. They are multipotent and can differentiate into a variety of specified cells, which could be useful for tissue engineering. They also possess the unique ability to travel to tumor sites and alter the microenvironment by inhibiting the processes that control tumor development. Previous data has confirmed this, but there isn’t enough evidence to date that supports whether MSCs can influence cancer epigenomes. In addition, MenSCs have only been shown to block ovarian cancer growth, and little is known on how these stem cells will react in other cancers.

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In the current study, the research team sought to investigate whether MenSCs can alter epigenetic regulation in hepatocellular carcinoma (HCC), a common type of liver cancer. Adopting to use a multi-platform approach for the analysis, they scrutinized genome-wide 5-mc and 5-hmc levels after MenSC therapy. HCC was chosen because its pathogenesis closely correlates with epigenetic dysregulation under long-term infection and chronic inflammation. Plus, genetically modified MSCs have proven to exhibit a beneficial effect on this disease. 

Using menstrual blood donated from healthy human females, the researchers conducted their study on liver cancer cell lines HepG2 and HuH-7, along with human fibroblast MRC-5. Epigenetic changes in HCC by MenSC were then examined using immunofluorescence, ELISA, and RT-PCR assays. The suppressive influence of MenSC on HCC was further examined in vitro, and genome-wide DNA methylation and hydroxymethlation in HCC cells after MenSC treatment were recorded.

The overall results of the study showed that MenSC could regulate the epigenetic mechanisms of HCC. As reported, “MenSCs exert an inhibitory effect on HCC growth via regulating 5-hmC and 5-mC abundance in the regulatory regions of oncogenic pathways including PI3K/AKT and MAPK signaling, especially in enhancers and promoters.”

While more research is needed to validate the results from this study, the findings do present evidence that explains the underlying mechanisms involved in crosstalk between cancer and MSCs. Furthermore, the data also points out that because MSCs sourced from menstrual blood epigenetically act as anticancer carrying molecules, they could be suitable for a modified MSC approach or combination treatment with chemotherapeutic agents.

Source: Wu, Y et al. (May 2019). Genome-wide DNA methylation and hydroxymethylation analysis reveal human menstrual blood-derived stem cells inhibit hepatocellular carcinoma growth through oncogenic pathway suppression via regulating 5-hmC in enhancer elements. Stem Cell Research & Therapy. 10(1):151.

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