Abstract LB-289: Polarization of adipose-derived mesenchymal stem cells by toll-like receptors stimulation

• Published in: Cancer research (Chicago, Ill.) Ill.), 2018-07, Vol.78 (13_Supplement), p.LB-289-LB-289
• Main Authors: Rivera-Cruz, Cosette M., Huff, Krista, Figueiredo, Marxa L.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2018-LB-289

Mesenchymal stem cells (MSCs) are a potential tool for cell therapy because of their ability to home to injury sites, modulate immune responses, promote tissue repair, among other features. MSCs can also home to tumors, similarly to how they home to injury sites, and exert modulatory functions in the tumor microenvironment. However, the mechanisms by which MSCs affect tumor cells is not well understood, and apparent contradictory effects of MSC-tumor interactions can be found in the literature, claiming that MSCs either promote or repress tumor growth and cell migration. In recent years, it was shown that MSCs derived from bone marrow (BM-MSCs) can be polarized by Toll-like receptor (TLR) signaling into two phenotypes with opposite effects on tumor development. TLR4 signaling induces an immune activating MSC1 population shown to inhibit tumor growth and migration, whereas TLR3 signaling induces an immune suppressive MSC2 population that promotes tumor progression. Adipose-derived mesenchymal stem cells (ASCs) are important constituents of tumor microenvironments. Their ability to migrate into tumors make these cells a potential candidate for delivering immunotherapy against tumor progression. Although the MSC1 and MSC2 duality has not been reported for ASCs, we hypothesized that due to their similarity to bone marrow MSCs, that ASC share the polarization phenotype. To test our hypothesis, we stimulated, or primed, hASCs with TLR3 and TLR4 agonists and evaluated gene expression changes expected to occur, in accordance to the previously described MSC1 and MSC2 phenotypes. Upregulation of IL-8 was observed for hASCs primed towards the MSC1 phenotype. CCL5 and IP10 were upregulated in cells primed towards the MSC2 phenotype. These results suggest that a polarization of hASCs may occur in a similar way as previously shown for BM-MSCs. On the other hand, no changes were observed in the expression of TGFβ, IL-6 and other associated genes, hinting to cell lineage phenotypical differences upon TLR stimulation. In addition, some phenotypical differences have been observed across different donor cells and priming conditions, which could contribute to the immunomodulatory inconsistencies reported in the literature. Citation Format: Cosette M. Rivera-Cruz, Krista Huff, Marxa L. Figueiredo. Polarization of adipose-derived mesenchymal stem cells by toll-like receptors stimulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2