Abstract
Purpose: Several attempts have been made to identify the mechanisms by which mesenchymal stem cells (MSCs)-derived secretome exert anti-tumor or tumorigenic effects, but still further investigations are needed to explore this subject. Thus, in this study we want to examine the expression of different cytokines in secretome of hWJ-MSCs and their effects on cytokine expression profile of the MCF-7 tumor cells. Methods: The hWJ-MSCs were isolated and characterized according to the International Society for Cellular Therapy criteria. Then, secretome of hWJ-MSCs was collected and freeze-dried, and 20 mg/mL of the freeze-dried secretome was used to treat MCF-7 cancer cells for 48 hours. Afterwards, the expression levels of 12 cytokines including IL-1a, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17A, TNFα, IFNγ and GM-CSF in secretome of hWJ-MSCs alone as well as in supernatant of tumor cells before and after treatment with hWJ-MSCs secretome were evaluated. Results: Our results indicate that MCF-7 cells express significant amount of IL-6 and IL-8. Moreover, significant amounts of IL-1a, IL-1b, IL-8, IL-6 and GM-CSF were detected in secretome of hWJ-MSCs. Furthermore, IL-1a, IL-2 and IL-4 were expressed significantly by MCF-7 cells after their treatment with hWJ-MSCs-derived secretome. Conclusion: According to our findings, the hWJ-MSCs derived secretome contains different cytokines which can exert either anti-tumor or tumorigenic effects.
Highlights
Cancer is a leading cause of mortality in human societies
The antitumor effects of the secretome of the human uterine tissue-derived stem cells conditioned media have been shown.[17]. These results indicate that the anti-tumor or protumorigenic effects of the mesenchymal stem cells (MSCs) derived secretome are both depended on the stem cells types which secretome obtained from, as well as the type of tumor.[17]
Our results show that secretion of IL-2 from MCF-7 cells in response to secretome of Wharton’s jelly stem cell as well as the secretion of GMCSF from stem cells themselves could lead to tumor regression.GM-CSF is essential for the differentiation of some cells and responsible for processing and presenting tumor antigens for the priming of antitumor cytotoxic T lymphocytes.[36]
Summary
Cancer is a leading cause of mortality in human societies. Different therapies such as chemotherapy, radiotherapy, hormone therapy and antibody based therapies are used for many types of cancers in the clinic.[1]. Many studies have shown that these cells can have both pro-tumorigenic and antitumor properties.[10,11,12,13] the use of these cells in the treatment of cancers acts like a double sword.[14] Among various sources of these cells, it has been shown that umbilical-cord MSCs (hWJ-MSCs) can inhibit tumor cells growth.[6,15] One of the important features of these cells that distinguishes them from other types is the high capacity of such cells to replicate.[16] hWJ-MSCs can be cultured and reproduced in large scales and could be used for treatment from allogeneic donors.[6] One of the most important characteristics of these cells, which cause their allogeneic application, is their low immunogenicity These cells express MHC-I molecules, while they do not express MHC-II molecules.[16] these cells have high tropism toward inflammatory environments like tumor microenvironment.[17] Due to concerns about the potential pro-tumorigenic effects of these cells, various studies have shown that secretome and exosomes derived from these
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