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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: 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.

One of the most intricate infertility problems among women is the number and quality of the oocytes. Menstrual blood-derived stem cells (MenSCs) are a recently discovered source of mesenchymal stem cells which is known as a suitable source of cells for regenerative medicine. We aimed to investigate whether MenSCs as autologous cell source from endometriosis, PCOS, and healthy women have different characteristics regarding their morphology, CD marker expression pattern, differentiation potential into oocyte-like cells, and oocyte-related genes expression. Menstrual blood samples (1-2 ml) from healthy and infertile women (PCOS and endometriosis) in the age range of 22-35 years were collected. Isolated MenSCs by the Ficoll-Paque density-gradient centrifugation method was characterized by flow cytometry. MenSCs were induced under 20 % follicular fluid (FF), and then they were evaluated for differentiation by Real time-PCR and immunocytochemistry assay. MenSCs derived from endometriosis women had different morphology from PCOS and healthy women, but similar regarding their CD marker pattern. All induced MenSCs showed morphological changes and expressed oocyte related genes (STELLA, GDF9, STRA8, PRDM, LHR, FSHR, SCP3, DDX4, and ZP2) in the 2nd week of culture, but there was a significant difference between the groups. Endometriosis-derived MenSCs showed higher levels of both gene and protein expressions. These findings propose that MenSCs derived from endometriosis and PCOS patients under 20 % FF, not only could differentiate into oocyte-like cells, but also showed more differential potential in comparison with healthy women. This indicates the possibility of using the patients' own MenSCs to differentiate into the oocyte-like cells.

Stem cells are unique cells obtained from a broad range of tissues with different features related to proliferation capability and differentiation capacity As one of the most important stem cell types in medicine today umbilical cord blood ndash derived stem cells UCB SCs are a more practical choice than embryonic stem cells because their use does not involve ethical issues For example these cells are a powerful tool used in cell based therapy and regenerative medicine to treat cancer and neurological autoimmune cardiovascular and blood diseases In this article we perform a mini review of umbilical cord blood ndash derived stem cells as an effector option in cell based therapy and regenerative medicine

Breast cancer is the most frequent cancer among women worldwide. Tumor immunology suggests relationships between the immune system, chronic inflammation, and cancer. The immune system may either prevent or promote carcinogenesis. Here, we evaluated molecular signaling pathways common in inflammation and cancer and detected the microRNAs which play pivotal roles in mediating these pathways. Using bioinformatics assays, signaling pathways common in inflammation and cancer, and microRNAs mediating these pathways were identified. MiR-590 was selected and cloned into the pLenti-III-eGFP vector and transfected into the breast cancer cell lines. The expression level of microRNA and the candidate genes was evaluated by real-time quantitative reverse transcription polymerase chain reaction, and the apoptosis level in transfected cells was measured by Annexin V-7AAD assay. The cell migration was tested by real-time quantitative reverse transcription polymerase chain reaction for MMP2/MMP9. The expression levels of miR-590 and the selected genes (i.e. JAK2, PI3K, MAPK1, and CREB) were measured 72 h after transfection. While miR-590 showed an over-expression, the genes were significantly down-regulated. A significant increase was observed in apoptosis level in both cell lines and MMP2/MMP9 was significantly decreased in MDA-MB-231 cells. MiR-590 was selected as a microRNA which triggers and down-regulates critical genes of signaling pathways similar in cancer and inflammation. Following the miR-590 treatment, JAK2, PI3K, MAPK1, and CREB were down-regulated and the apoptosis level was increased in breast cancer cell lines. Apparently, some microRNAs can be good candidates for novel treatments of cancer. Although miR-590 showed good results in this study, further studies are required to investigate the role of miR-590 in breast cancer therapy.

Background : Polycystic ovarian syndrome (PCOS) is a low-grade inflammatory disease characterized by hyperandrogenemia, hirsutism, chronic anovulation and vascular disorder. Interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are triggered by inflammatory stimuli and lead to angiogenesis and pathogenesis of the ovary. Honeybee venom (HBV) contains an array of biologically active components possessing various pharmaceutical properties. This study was designed to assess the possibility of HBV application as an anti-inflammatory therapeutic agent to suppress levels of the main inflammatory mediators IL-6, COX-2 and VEGF. To induce PCOS, 1 mg of estradiol valerate (EV) per 100 g of body weight was subcutaneously (SC) injected into eight-week-old rats. After 60 days, 0.5 mg/kg of HBV was administered Intraperitoneal (IP) for 14 consecutive days, and the results of PCOS treatment were investigated. Rats were then anesthetized with CO2, and the ovaries were surgically removed. Serum IL-6 was detected by the ELISA kit. Immunoexpression of COX-2 and VEGF were examined in three groups: EV-induced PCOS, HBV-treated PCOS and control animals. Results : Thickness of theca layer, number and diameter of cysts and levels of IL-6 significantly decreased in HBV group relative to PCOS group. The immunohistochemical analysis showed an increase in COX-2 and VEGF expression in PCOS group whereas HBV-treated rats presented weak and irregular immunostaining. Conclusions : Our results suggest that the beneficial effect of HBV may be mediated through its inhibitory effect on serum IL-6 level and ovarian COX-2 and VEGF expression.