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.

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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Long noncoding RNAs (lncRNAs) are prominent as crucial regulators of tumor establishment and are repeatedly dysregulated in multiple cancers. Therefore, lncRNAs have been identified to play an essential function in carcinogenesis and progression of cancer at genetic and epigenetic levels. FENDRR (fetal-lethal noncoding developmental regulatory RNA) as an LncRNA is a hallmark of various malignancies. FENDRR is crucial for multiple organs' development such as lung and heart. The effects of FENDRR under signaling pathways in different cancers have been identified. In addition, it has been verified that FENDRR can affect the development and progression of various cancers. In addition, FENDRR expression has been associated with epigenetic regulation of target genes participating in tumor immunity. Furthermore, FENDRR downregulation was observed in various types of cancers, including colorectal cancer, gastric cancer, pancreatic cancer, cholangiocarcinoma, liver cancer, gallbladder cancer, lung cancer, breast cancer, endometrial cancer, prostate cancer, chronic myeloid leukemia, osteosarcoma, and cutaneous malignant melanoma cells. Here, we review the biological functions and molecular mechanisms of FENDRR in several cancers and, we will discuss its potential as a cancer biomarker and as a probable option for cancer treatment.

: Crohn's disease (CD) which usually leads to anal fistulas among patients is the most important inflammatory bowel disease that causes morbidity in many people around the world. This review article proposes using MSCs as a hopeful therapeutic strategy for CD and anal fistula treatment in both preclinical and clinical conditions. Finally, Darvadstrocel - a cell based medication to treat complex anal fistulas in adults- as the only European Medicines Agency (EMA)-approved product for the treatment of anal fistulas in CD is addressed. Although several common therapies such as surgery and anti-tumor necrosis factor-alpha (TNF-α) drugs as well as a combination of these methods is used to improve this disease, however, due to the low effectiveness of these treatments, the use of new strategies with higher efficiency is still recommended. Cell therapy is among the new emerging therapeutic strategies that have attracted great attention from clinicians due to its unique capabilities. One of the most widely used cell sources administrated in cell therapy is mesenchymal stem cell (MSC). This review article will discuss preclinical and clinical studies about MSCs as a potent and promising therapeutic option in the treatment of CD and anal fistula.

Background: One of the most important involved factors in pregnancy occurrence following intrauterine insemination (IUI) is semen sample preparation. Recently, supernatant product of adipose tissue derived mesenchymal stem cells (SPAS) method has been shown to improve semen parameters. Objective: To compare the effect of preparation methods in order to IUI, SPAS and density gradient centrifugation (DGC). Materials and Methods:This trial was done on 80 couples with male factor infertility who attend jihad daneshgahi infertility treatment center of Qom province, undergoing ovarian stimulation and IUI cycle. Various semen parameters including motility, count, DNA fragmentation and capacitation were evaluated before and after preparation. The effect of semen preparation methods and influence of various semen parameters on pregnancy occurrence were examined. Results: The overall clinical pregnancy rate was 17.5% per patient with no miscarriage. The pregnancy rate for DGC and SPAS were 5% (2 of 40) and 30% (12 of 40) respectively. Since there is no significant difference in improving motion parameters between two groups (except recovery of total number of motile spermatozoa), it seems that these parameters alone are not sufficient to predict IUI pregnancy outcome whereas in samples with >25 million motile spermatozoa in inseminate, there was a clear trend for a higher pregnancy rate for the sample processed using SPAS. Conclusion: Considering SPAS as a new and effective method leading to provide a combination of various improved semen parameters, is expected in near future.

Background: Male factor infertility that is the cause of about half of the infertility cases, may occur due to azoospermia. Because spermatogenesis defects may lead to non-obstructive azoospermia (NOA), investigating the factors involved in spermatogenesis, including hormones and genes, is one of the most important aspects in understanding the mechanism of NOA in men. Objectives: Male infertility is a complex disorder that affects a large proportion of men, yet many of its causes are unknown. Clarifying its genetic basis may help to identify the causes of infertility and provide effective treatment for patients. Methods: In this case-control study, single nucleotide polymorphisms (SNPs) located in the USP9Y gene were investigated. Accordingly, 100 healthy men and 100 NOA patients were regarded as control and case groups, respectively. Testis tissue samples were taken during the testicular sperm extraction (TESE) procedure, DNA extraction was done, and ARMS PCR was designed and performed. The rs3212292, rs2032597, rs2032604, rs2032598, and rs717268 polymorphisms in the USP9Y gene were analyzed by Tetra-ARMS PCR. Furthermore, the serum levels of sex hormones were assessed by the ELISA technique. Finally, the obtained data were analyzed by SPSS software. Results: According to the obtained results, there was no significant difference in case of genotype frequency of investigated SNPs between the case and control groups (P ≥ 0.05). The mean FSH and LH levels in the control group were relatively lower than the case group (P ≤ 0.05), whereas no significant difference in the mean testosterone level was observed between the two groups (P ≥ 0.05). Conclusions: Polymorphisms of the assessed SNPs showed no effect on the frequency of azoospermia; thus, polymorphisms did not increase the risk of NOA and also did not have a protective effect against the disease. Also, the results showed that the serum levels of FSH and LH increased in NOA patients.