Background. Despite recent advances in scientific knowledge and clinical practice, management, and treatment of breast cancer, as one of the leading causes of female mortality, breast cancer remains a major burden. Recently, methods employing stem cells and their derivatives, i.e., exosomes, in gene-based therapies hold great promise. Since these natural nanovesicles are able to transmit crucial cellular information which can be engineered to have robust delivery and targeting capacity, they are considered one of the modes of intercellular communication. miR-145, one of the downregulated microRNAs (miRNAs) in various cancers, can regulate tumor cell invasion, metastasis, apoptosis, and proliferation and stem cell differentiation. Objectives. The aim of this study was to investigate the role of exosomes secreted from adipose tissue-derived mesenchymal stem cells (MSCs) for miR-145 transfection into breast cancer cells in order to weaken their expansion and metastasis. Methods. Here, we exploited the exosomes from adipose tissue-derived mesenchymal stem cells (MSC-Exo) to deliver miR-145 in the T-47D breast cancer cell line. Lentiviral vectors of miR-145-pLenti-III-enhanced green fluorescent protein (eGFP) and empty pLenti-III-eGFP as the backbone were used to transfect MSCs and T-47D cells. In order to find the efficiency of exosomes as a delivery vehicle, the expression level of some miR-145 target genes, including Rho-Associated Coiled-Coil Containing Protein Kinase 1 (ROCK1), Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2), Matrix Metalloproteinase 9 (MMP9), and Tumor Protein p53 (TP53), was compared in all treatment groups (T-47D cells treated by miR-145-transfected MSCs and their derivatives or their backbone) and control group (untransfected T-47D cells) using real-time PCR. Results. The obtained data represented the inhibitory effect of miR-145 on apoptosis induction and metastasis in both direct miR-treated groups. However, exosome-mediated delivery caused an improved anticancer property of miR-145. Conclusion. Restoration of miR-145 using MSC-Exo can be considered a potential novel therapeutic strategy in breast cancer in the future.
Background. Research into the pathogenesis of endometriosis would substantially promote its effective treatment and early diagnosis. Currently, accumulating evidence has shed light on the importance of endometrial stem cells within the menstrual blood which are involved in the establishment and progression of endometriotic lesions in a retrograde manner. Objectives. We aimed to identify the differences in some genes’ expression between menstrual blood-derived mesenchymal stem cells (MenSCs) isolated from endometriosis patients (E-MenSCs) and MenSCs from healthy women (NE-MenSCs). Methods. Menstrual blood samples (2-3 mL) from healthy and endometriosis women in the age range of 22–35 years were collected. Isolated MenSCs by the Ficoll-Paque density-gradient centrifugation method were characterized by flow cytometry. MenSCs were evaluated for key related endometriosis genes by real-time-PCR. Results. E-MenSCs were morphologically different from NE-MenSCs and showed, respectively, higher and lower expression of CD10 and CD9. Furthermore, E-MenSCs had higher expression of Cyclin D1 (a cell cycle-related gene) and MMP-2 and MMP-9 (migration- and invasion-related genes) genes compared with NE-MenSCs. Despite higher cell proliferation in E-MenSCs, the BAX/BCL-2 ratio was significantly lower in E-MenSCs compared to NE-MenSCs. Also, the level of inflammatory genes such as IL1β, IL6, IL8, and NF-κB and stemness genes including SOX2 and SALL4 was increased in E-MenSCs compared with NE-MenSCs. Further, VEGF, as a potent angiogenic factor, showed a significant increase in E-MenSCs rather than NE-MenSCs. However, NE-MenSCs showed increased ER-α and β-catenin when compared with E-MenSCs. Conclusion. Here, we showed that there are gene expression differences between E-MenSCs and NE-MenSCs. These findings propose that MenSCs could play key role in the pathogenesis of endometriosis and further support the menstrual blood retrograde theory of endometriosis formation. This could be of great importance in exploiting promising therapeutic targets and new biomarkers for endometriosis treatment and prognosis.
Polycystic ovarian syndrome (PCOS) is a low grade inflammatory disease characterized by hyperandrogenemia and chronic anovulation. C-reactive protein (CRP), released by adipocytes, plays a key role in PCOS. Apis mellifera honeybee venom (HBV) contains a variety of biologically active components with various pharmaceutical properties. This study was designed to assess the possibility of HBV application as an anti-inflammatory therapeutic agent. To induce PCOS, 1 mg/100 g body weight estradiol valerate (EV) was subcutaneously (SC) injected into eight-week-old rats. After 60 days, 0.5 mg/kg HBV was administered SC for 14 consecutive days, and the results of PCOS treatment were investigated. Rats were then anesthetized with chloroform, and their ovaries and livers were surgically removed to determine histomorphometrical changes. Testosterone and 17-β-estradiol were detected by chemiluminescence immunoassay. In order to detect serum CRP, ELISA kit was used in three groups of EV-induced PCOS, HBV-treated PCOS and control animals. Thickness of the theca layer, number of cysts and the level of serum CRP significantly decreased in HBV group in comparison with PCOS group. Moreover, corpus luteum, as a sign of ovulation, was observed in HBV-treated ovaries which were absent in PCOS group. Our results suggest that the beneficial effect of HBV may be mediated through its inhibitory effect on serum CRP levels.
Background. Exosomes as extracellular vesicles (EVs) are nanoscale intercellular messengers secreted from cells to deliver biological signals. Today, exosomes have become a new field of research in regenerative medicine and are considered as potential therapies to control inflammation and wound healing and enhance and improve healing in many diseases. Given the global burden of osteoarthritis (OA) as the fastest-growing health condition and one of the major causes of physical disability in the aging population, research to establish EVs as therapeutic products can meet the basic clinical needs in the management of osteoarthritis and provide a therapeutic solution. Objectives. The present study is aimed at evaluating the regenerative potentials of the exosomes secreted from adipose and bone marrow tissue-derived mesenchymal stem cells (AD- and BM-MSCs) in ameliorating the symptoms of OA. Method. In this experimental study, AD- and BM-MSCs were isolated and cultured in the laboratory until passage 3. Finally, these cells’ secreted exosomes were isolated from their conditioned medium. Ciprofloxacin-induced OA mouse models underwent intra-articular injection of exosomes from AD-MSCs and BM-MSCs. Finally, the expression levels of collagen I and II, sox9, and aggrecan genes using real-time PCR, histological analysis, and immunohistochemical (IHC) studies were performed. Results. Real-time PCR data showed that although the expression level of collagen type II was lower in both exosome-treated groups than the normal, but it was significantly increased in comparison with the sham and OA, with higher expression in BM-Exo rather than AD-Exo group. Similarly, the histological staining and IHC results have provided almost identical data, emphasizing on better therapeutic effect of BM-MSCs-exosome than AD-MSCs-exosome. Conclusion. BM-MSCs secreted exosomes in comparison with AD-MSCs could be considered as a better therapeutic option to improve osteoarthritis and exhibit potential as a disease-modifying osteoarthritis cell-free product.
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