Comparative immunomodulatory properties of mesenchymal stem cells derived from human breast tumor and normal breast adipose tissue

人类乳腺肿瘤和正常乳腺脂肪组织间充质干细胞的免疫调节特性比较

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作者:Koushan Sineh Sepehr, Alireza Razavi, Zuhair Mohammad Hassan, Abdolreza Fazel, Meghdad Abdollahpour-Alitappeh, Majid Mossahebi-Mohammadi, Mir Saeed Yekaninejad, Behrouz Farhadihosseinabadi, Seyed Mahmoud Hashemi

Conclusion

MSCs educated in stage II breast cancer and normal breast adipose tissue, although sharing a similar morphology and immunophenotype, exhibited a clearly different profile in some immunomodulatory functions and protein secretions.

Methods

T-MSCs and N-MSCs were isolated by the explant culture method and characterized, and their immunomodulatory function was assessed on peripheral blood lymphocytes (PBLs) by evaluating the effects of MSC conditioned media on the proliferation and induction of some cytokines and regulatory T cells (Tregs) by BrdU assay, ELISA, and flow cytometry. In addition, we compared the secretion of indoleamine 2,3-dioxygenase (IDO), vascular endothelial growth factor (VEGF), matrix metallopeptidase (MMP)-2, MMP-9, and Galectin-1.

Objective

Mesenchymal stem cells (MSCs), one of the most important stromal cells in the tumor microenvironment, play a major role in the immunomodulation and development of tumors. In contrast to immunomodulatory effects of bone marrow-derived MSCs, resident MSCs were not well studied in tumor. The aim of this study was to compare the immunomodulatory properties and protein secretion profiles of MSCs isolated from breast tumor (T-MSC) and normal breast adipose tissue (N-MSC). Materials and

Results

T-MSCs showed a higher secretion of transforming growth factor beta (TGF-β), prostaglandin E2 (PGE2), IDO, and VEGF and lower secretion of MMP-2 and MMP-9 compared with N-MSCs. However, no significant difference was found in the secretion of interferon gamma (IFN-γ), interleukin 10 (IL10), IL4, IL17, and Galectin-1 in T-MSCs and N-MSCs. The immunomodulatory effect of soluble factors on PBLs showed that T-MSCs, in contrast to N-MSCs, stimulate PBL proliferation. Importantly, the ability of T-MSCs to induce IL10, TGF-β, IFN-γ, and PGE2 was higher than that of N-MSCs. In addition, T-MSCs and N-MSCs exhibited no significant difference in Treg induction.

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