Tumor associated mesenchymal stromalcells show higher immunosuppressiveand angiogenic properties compared toadipose derived MSCs

Background: Differentiation, migratory properties and availability of MesenchymalStromal Cells [MSC] have become an important part of biomedical research. However,the functional heterogeneity of cells derived from different tissues has hamperedproviding definitive phenotypic markers for these cells

Objective: To characterize andcompare the phenotype and cytokines of adipose derived MSCs [AD-MSCs] andtumoral-MSCs [T-MSCs] isolated from mammary tumors of BALB/c mice

Methods:Immunophenotyping and in vitro differentiation tests were used for MSCcharacterization. Cytokine and enzyme profiles were assessed using ELISA and RealtimePCR, respectively

Results: T-MSCs expressed significantly higher levels of HLADR[p=0.04]. Higher levels of PGE2 and COX-2 enzyme were also observed in TMSCs[p=0.07 and p=0.00, respectively]. Additionally, T-MSCs expressed higher levelsof iNOS and MMP9 [p=0.01 and p=0.01, respectively]. T-MSCs were also able toinduce higher levels of proliferation and migration of HUVEC endothelial cells inwound scratch assay compared to AD-MSCs [p=0.015]

Conclusion: Functionaldifferences showed by the surface markers of MSCs, cytokine and enzyme productionindicate the effect of different microenvironments on MSCs phenotype and function

Comparative study of the effect of LPS on the function of BALB/c and C57BL/6 peritoneal macrophages

Macrophages influence their environment and surrounding immune cells as soon as stimulators affect them. Different sources of macrophages induce different reactions in their neighboring immune cells,which result in non-uniform immunologic outcomes. In this experimental research, we compare the behavior of peritoneal macrophages to lipopolysaccharide [LPS] stimulation from BALB/cmice as an indicator of a type 2 immune response and from C57BL/6 mice as an indicator of a type 1 immune response. In this experimental study, peritoneal macrophages prepared from thioglycolate stimulated BALB/c and C57BL/6 micewere treated with 1microg/ml LPS. At different time points after LPS treatment, nitric oxide [NO], interferon gamma [IFN-gamma]. interleukin 4 [IL-4],transforming growth factor beta[1] [TGF-beta[1]], interleukin 17 [IL-17], and interleukin 10[IL-10] production were measured in the supernatants of all macrophage cultures.Indoleamine 2, 3 dioxygenase [IDO] and phagocytic activitywere analyzed in the different experimental groups. The supernatant effects of LPS-treated macrophages on splenocyte proliferation was assessed by the colorimetric method using a 3-[4,5-Dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide [MTT] reagent. According to cytokine analysis, different mouse strains show different cytokine patterns in response to LPS. C57BL/6 macrophages produced more IL-17, IL-10, and IFN-gamma while BALB/c macrophages produced more TGF-beta[1]., and IL-4. There was no significant difference in IDO activity between strains [p

Long acting propranolol and HSP-70 rich tumor lysate reduce tumor growth and enhance immune response against fibrosarcoma in Balb/c mice

Noradrenaline [NA], the principal neurotransmitter released from sympathetic nerve terminals, influences T-cell maturation, not only directly in developing T cells, but also indirectly, by acting on the thymic nonlymphoid cells. In vitro and in vivo studies have demonstrated the anti-proliferative, anti-migratory, antiangiogenic and cytotoxic properties of propranolol, beta-AR blocker, against various cancers. To evaluate the effect of propranolol on efficacy of HSP-70 rich lysate vaccine in immunotherapy of fibrosarcoma. Mouse fibrosarcoma WEHI-164 cells were used to immunize tumor-bearing mice with or without propranolol and HSP-70. Splenocytes proliferation, cytotoxic activity of the splenocytes, naturally occurring CD4+ CD25[high] T-reg cells and IFN-gamma and IL-4 secretion as well as tumor size, were assessed to describe the anti-tumor immune response. A significant increase in the level of IFN- gamma in the mice vaccinated with WEHI-164 cells enriched with HSP-70 and co-treated with propranolol was observed compared to controls. However, HSP enrichment or propranolol treatment alone did not enhance the immune response as measured by the level of IFN-gamma. Likewise, a decrease in tumor growth in the test group [p<0.01] and a significant increase in CTL activity [p<0.05] was observed. HSP enriched vaccine shows anti-tumor activity, probably due to the modulation of immune responses