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OBJECTIVES: Controversial results have been reported regarding the anti-tumor properties of extracellular vesicles derived from mesenchymal stem cells (MSCs). The present study was conducted to evaluate whether secretome derived from Human Wharton's jelly mesenchymal stem cells (hWJMSCs) may stimulate or inhibit breast cancer growth in vitro and in vivo. MATERIALS AND METHODS: MTT assays was performed to determine anti-tumor effects of hWJMSCs-secretome on both MCF-7 and 4T1 tumor cells in vitro. Afterward, 4T1 breast tumors were established in different groups of Balb/C mice (12 mice/group). The tumor sizes were monitored in different treatment groups and at day 30 post-tumor inoculation (PTI), blood samples were obtained and 6 mice of each group were sacrificed for hematological and histopathological assays. The rest of the mice in each group (n=6) were left alive up to day 120 PTI to determine survival rate. RESULTS: We found that hWJMSCs-secretome can inhibit growth of MCF-7 and 4T1 tumor cell lines in vitro. Moreover, intratumoral administration of hWJMSCs-secretome resulted in significant tumor growth inhibition and improvement of hematological indices in vivo and prolonged survival rate of tumor bearing mice. CONCLUSION: According to our findings, hWJMSCs-secretome could be considered a potent anti-tumor agent, however, further investigation should be done on other cancer models.

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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.

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Nowadays, Mesenchymal stem cells (MSCs) have become one of the most attractive tools for treating tumors, due to their specific characteristics, the most prominent of which are tropism toward tumor. These cells will exert their effects through their secretion. In this study, our aim was to evaluate the anti-cancer effect of umbilical cord-derived mesenchymal cells (UCMSC) secretome, on MCF-7 tumor cells. MSCs were extracted from the umbilical cord of mothers, having normal delivery or cesarean section. After culture, the supernatants of these cells were collected and freeze-dried. The cytotoxic effect of freeze-dried secretome was examined at different concentrations on MCF-7 and the optimum concentrations (IC50) were calculated, using MTT assay. These results were confirmed by BrdU assay. The effect of induction of apoptosis of the MSC secretome on MCF-7 was determined, using annexin V/PI method by flow cytometry. The results of our study indicate that the isolation and growth time of UCMSCs of mothers who were naturally delivered was lower than those who received cesarean section. Co-culture studies showed that MSCs had cytotoxic effects on MCF-7 cells. The MSC secretome also showed cytotoxic effects on the MCF-7 cell line, this effect was mediated by induction of apoptosis, which was dose-dependent with an IC50 of 10 mg/mL.

Asunto(s)

Neoplasias de la Mama/terapia , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Cordón Umbilical/citología , Apoptosis , Técnicas de Cultivo de Célula , Movimiento Celular , Técnicas de Cocultivo , Medios de Cultivo/química , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Concentración 50 Inhibidora , Células MCF-7

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BACKGROUND: Given miscarriage psychological consequences on the women health, the aim of the present study is the survey of effectiveness rate of attributive retraining interventions on women depression and anxiety reducing after miscarriage. METHODS: The present study is semi-empiric and it's made using control group, pre- and post-test execution and follow-up. Thirty-two women, who had recent experience of miscarriage, were selected among female referents to obstetricians and clinics in Esfahan city by accessible sampling and then they were placed on two groups, case and control, randomly. Case group participated in 6 weekly sessions for attributive retraining interventions and both groups completed hospital depression and anxiety questionnaire on three steps: Pre-test, post-test, and follow-up. Collected data were analyzed statistically, using Statistical Package for the Social Sciences (SPSS) software and variance by repeated measuring. RESULTS: Obtained results show that average post-test and follow-up scores of depression and anxiety in case group is less than average post-test scores in control group, significantly (P < 0.0005). CONCLUSIONS: The findings of this research, "Attributive Retraining Effectiveness on Women's Depression and Anxiety Reducing after Miscarriage," were confirmed.

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BACKGROUND: In some studies, the involvement of dangerous psychological and behavioral factors in etiology and physiotherapy of vascular disturbances have been shown. In other studies, the relationship between the personality type and increase in cardiovascular disease has been demonstrated. The type D personality is defined as having two characteristics of negative affect and social inhibition. It is thought that individuals with type D personality are at increased risk of carotid artery intima-media thickening which predisposes them to vascular disease that is one of the most important factors for the stroke. In this study, we try to determine whether type D personality is a contributing factor to an increase in the intima-media of the carotid artery. This study was done in 2012 in the teaching hospital of Alzahra in Isfahan Iran. METHODS: This is a case/control study which is done at Alzahra hospital in Isfahan in 2011-12. The statistical population in this study is composed of individuals who do not have any risk factors for stroke and are randomly selected among the hospital staff or the patient's family members who accompanied the patient at the hospital. They filled out a questioner that would assist in detecting type D personality. A carotid Doppler ultrasound that measures the intima-media thickness in the selected individuals was performed. The information obtained from the study was evaluated by Statistical Product and Service Solutions (SPSS) software and the intima-media thicknesses were compared in two groups of patients. RESULTS: The average thickness of intima media in two groups, consist of placebo and patients, was 0.739 ± 0.12 and 0.759 ± 0.14 millimeter, respectively. There was no meaningful difference between the two groups based on t-test values (P = 0.19). It is important to note that based on the results, 22.9% of placebos and 48.6% of individuals with type D personality presented with abnormal thickness. The difference between the two groups were meaningful based on Chi-Squared test (P = 0.001). CONCLUSIONS: We conclude that type D personality increases the risk of cardiovascular diseases specially the stroke and myocardial infarction due to the higher prevalence of hormonal imbalances leading to arterial vasospasm and atherosclerotic disease. As a result, it is necessary to evaluate and treat these patients due to increased risk of atherosclerotic diseases, stoke, and myocardial infarction.