Secretome of aggregated embryonic stem cell-derived mesenchymal stem cell modulates the release of inflammatory factors in lipopolysaccharide-Induced peripheral blood mononuclear cells

Background: Bone marrow mesenchymal stem cells [BM-MSCs] have emerged as a potential therapy for various inflammatory diseases. Because of some limitations, several recent studies have suggested the use of embryonic stem cell-derived MSCs [ESC-MSCs] as an alternative for BM-MSCs. Some of the therapeutic effects of the ESCMSCs are related to the secretion of a broad array of cytokines and growth factors, known as secretome.Harnessing this secretome for therapeutic applications requires the optimization of production of secretary molecules. It has been shown that aggregation of MSCs into 3D spheroids, as a preconditioning strategy, can enhance immunomodulatory potential of such cells. In this study, we investigated the effect of secretome derived from human ESC-MSCs [hESC-MSCs] spheroids on secretion of IL-1Beta, IL-10, and tumor necrosis factor Alpha [TNF-Alpha] from lipopolysaccharide [LPS]-induced peripheral blood mononuclear cells [PBMCs]

Methods: In the present study, after immunophenotyping and considering mesodermal differentiation of hESC-MSCs, the cells were nonadherently grown to prepare 3D aggregates, and then conditioned medium or secretome was extracted from the cultures. Afterwards, the anti-inflammatory effects of the secretome were assessed in an in vitro model of inflammation

Results: Results from this study showed that aggregate-prepared secretome from hESC-MSCs was able to significantly decrease the secretion of TNF-Alpha [301.7 +/- 5.906, p < 0.0001] and IL-1 Alpha [485.2 +/- 48.38, p < 0.001] from LPS-induced PBMCs as the indicators of inflammation, in comparison with adherent culture-prepared secretome [TNF-Alpha : 166.6 +/- 8.04, IL-1Beta: 125.2 +/- 2.73]

Conclusion: Our study indicated that cell aggregation can be an appropriate strategy to increase immunomodulatory characteristics of hESC-MSCs

Hypoxia pre-conditioned embryonic mesenchymal stem cell secretome reduces IL-10 production by peripheral blood mononuclear cells

Background: Mesenchymal stem cells [MSCs] are important candidates for MSC-based cellular therapy. Current paradigm states that MSCs support local progenitor cells in damaged tissue through paracrine signaling. Therefore, the study of paracrine effects and secretome of MSCs could lead to the appreciation of mechanisms and molecules associated with the therapeutic effects of these cells. This study analyzed anti-inflammatory and immune-modulatory effects of MSC secretomes derived from embryonic stem cells [ESCs] and bone marrow cells after hypoxia and normoxia preconditioning

Methods: ESCs differentiated into MSCs and characterized by flow cytometry as well as by differentiation into adipocytes and osteoblasts. The experimental groups were consisted of individual groups of ESC-MSCs and BM-MSCs [bone marrow-derived mesenchymal stromal cells], which were preconditioned with either hypoxia or normoxia for 24, 48 and 72 h. After collecting the cell-free medium from each treatment, secretomes were concentrated by centrifugal filters. Using a peripheral blood mononuclear cell [PBMC] assay and ELISA, IL-10 concentration in PBMCs was evaluated after their incubation with different secretomes from preconditioned and non-preconditioned MSCs

Results: A significant difference was observed between ESC-MSC normoxia and ESC-MSC hypoxia in IL-10 concentration, and normoxia secretomes increased IL-10 secretion from PBMCs. Moreover, the strongest IL-10 secretion from PBMCs could be detected after the stimulation by ESC-MSC conditioned secretomes, but not BM-MSC conditioned medium

Conclusions: Human hypoxia preconditioned ESC-MSC secretome indicated stronger immune-modulatory effects compared to BMMSC conditioned medium. It could be suggested that induced MSCs confer less immune-modulatory effects but produce more inflammatory molecules such as tumor necrosis factor alpha, which needs further investigation

YKL-40 gene expression and plasma levels of CD30 are not affected by isoflurane or propofol: pilot study

Background: It has been hypothesized that the body's response to anesthesia techniques can increase risk of cancer recurrence and metastatic disease after surgery and also can modulate immune responses. Some acute inflammatory markers have been measured to survey the immunomodulatory effect of anesthesia, but in this research, we studied the plasma level of CD30 and YKL-40 gene expression which can present major changes of the immune system

Materials and Methods: Our study was a controlled before and after study. 34 women with biopsy-proven breast cancer were randomized to receive either propofol general anesthesia [n=17] or standard isoflurane general anesthesia [n=17]. There were no significant differences between the two patient groups in age, body weight, and height, length of general anesthesia, operative time and group of surgery. The blood samples were collected in two different sets, before anesthesia and 72-h postoperatively. Soluble CD30 [sCD30] plasma level was measured by ELISA and YKL-40/CHI3L1 gene expression was evaluated by real-time-PCR

Results: The results showed that the anesthetics, propofol and isoflurane, have no effect on the expression of YKL-40. Despite increased in the expression of YKL-40 that was observed in patients receiving isoflurane, this increase was not statistically significant. There was no significant increase or decrease in plasma concentrations of sCD30

Conclusion: YKL-40 and sCD30 are not affected by isoflurane or propofol. So, in immunological perspective, there is no preference in use of isoflurane or propofol in breast cancer patients