Decidua Parietalis Mesenchymal Stem/Stromal Cells and Their Secretome Diminish the Oncogenic Properties of MDA231 Cells In Vitro.

Mesenchymal stem cells (MSCs) have been shown to suppress tumor growth, inhibit angiogenesis, regulate cellular signaling, and induce apoptosis in cancer cells. We have earlier reported that placenta-derived decidua parietalis mesenchymal stem/stromal cells (DPMSCs) not only retained their functional characteristics in the cancer microenvironment but also exhibited increased expression of anti-apoptotic genes, demonstrating their anti-tumor properties in the tumor setting. In this study, we have further evaluated the effects of DPMSCs on the functional outcome of human breast cancer cell line MDA231. MDA231 cells were exposed to DPMSCs, and their biological functions, including adhesion, proliferation, migration, and invasion, were evaluated. In addition, genomic and proteomic modifications of the MDA231 cell line, in response to the DPMSCs, were also evaluated. MDA231 cells exhibited a significant reduction in proliferation, migration, and invasion potential after their treatment with DPMSCs. Furthermore, DPMSC treatment diminished the angiogenic potential of MDA231 cells. DPMSC treatment modulated the expression of various pro-apoptotic as well as oncogenes in MDA231 cells. The properties of DPMSCs to inhibit the invasive characteristics of MDA231 cells demonstrate that they may be a useful candidate in a stem-cell-based therapy against cancer.

Conditions Mimicking the Cancer Microenvironment Modulate the Functional Outcome of Human Chorionic Villus Mesenchymal Stem/Stromal Cells in vitro.

Mesenchymal stem/stromal cells isolated from chorionic villi of human term placentae (CV-MSCs) possess unique biological characters. They exhibit self-renewal, directional migration, differentiation, and immunomodulatory effects on other cell lineages, by virtue of which they can be utilized as therapeutic carriers, for drug targeting, and therapy. Tumors display characteristic features of a damaged tissue microenvironment, which is saturated with conditions such as hypoxia, sustained inflammation, and increased oxidative stress. CV-MSCs function normally in a high oxidative stress environment induced by hydrogen peroxide (H2O2) and glucose and also protect endothelial cells from their damaging effects. For their therapeutic applications in a disease like cancer, it is necessary to ascertain the effects of tumor microenvironment on their functional outcome. In this study, we investigated the functional activities, of CV-MSCs in response to conditioned media (CM) obtained from the culture of breast cancer cell line MDA-231 (CM-MDA231). CV-MSCs were exposed to CM-MDA231 for different spatio-temporal conditions, and their biological functions as well as modulation in gene expression were evaluated. Effect of CM-MDA231 on factors responsible for changes in functional outcome were also investigated at the protein levels. CV-MSCs exhibited significant reduction in proliferation but increased adhesion and migration after CM-MDA231 treatment. Interestingly, there was no change in their invasion potential. CM-MDA231 treatment modulated expression of various genes involved in important cellular events including, integration, survival, message delivery and favorable outcome after transplantation. Analysis of pathways related to cell cycle regulation revealed significant changes in the expression of p53, and increased phosphorylation of Retinoblastoma (Rb) and Checkpoint Kinase 2 in CV-MSCs treated with CM-MDA231. To summarize, these data reveal that CV-MSCs retain the ability to survive, adhere, and migrate after sustained treatment with CM-MDA231, a medium that mimics the cancer microenvironment. These properties of CV-MSCs to withstand the inflammatory tumor like microenvironment prove that they may make useful candidate in a stem cell based therapy against cancer. However, further pre-clinical studies are needed to validate their therapeutic usage.

Preconditioning of Human Decidua Basalis Mesenchymal Stem/Stromal Cells with Glucose Increased Their Engraftment and Anti-diabetic Properties.

BACKGROUND: Mesenchymal stem/stromal cells (MSCs) from the decidua basalis (DBMSCs) of the human placenta have important functions that make them potential candidates for cellular therapy. Previously, we showed that DBMSC functions do not change significantly in a high oxidative stress environment, which was induced by hydrogen peroxide (H2O2) and immune cells. Here, we studied the consequences of glucose, another oxidative stress inducer, on the phenotypic and functional changes in DBMSCs. METHODS: DBMSCs were exposed to a high level of glucose, and its effect on DBMSC phenotypic and functional properties was determined. DBMSC expression of oxidative stress and immune molecules after exposure to glucose were also identified. RESULTS: Conditioning of DBMSCs with glucose improved their adhesion and invasion. Glucose also increased DBMSC expression of genes with survival, proliferation, migration, invasion, anti-inflammatory, anti-chemoattractant and antimicrobial properties. In addition, DBMSC expression of B7H4, an inhibitor of T cell proliferation was also enhanced by glucose. Interestingly, glucose modulated DBMSC expression of genes involved in insulin secretion and prevention of diabetes. CONCLUSION: These data show the potentially beneficial effects of glucose on DBMSC functions. Preconditioning of DBMSCs with glucose may therefore be a rational strategy for increasing their therapeutic potential by enhancing their engraftment efficiency. In addition, glucose may program DBMSCs into insulin producing cells with ability to counteract inflammation and infection associated with diabetes. However, future in vitro and in vivo studies are essential to investigate the findings of this study further.