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Recurrent pregnancy loss (RPL) is one of the most common complications of early pregnancy associated in most cases with local or systemic immune abnormalities such as the diminished proportion of regulatory T cells (Tregs). Mesenchymal stem cells (MSCs) have been shown to modulate immune responses by de novo induction and expansion of Tregs. In this study, we analyzed the molecular and cellular mechanisms involved in Treg-associated pregnancy protection following MSCs administration in an abortion-prone mouse mating. In a case-control study, syngeneic abdominal fat-derived MSCs were administered intraperitoneally (ip) to the DBA/2-mated CBA/J female mice on day 4.5 of pregnancy. Abortion rate, Tregs proportion in spleen and inguinal lymph n
Recurrent pregnancy loss (RPL) is one of the most common complications of early pregnancy associated in most cases with local or systemic immune abnormalities such as the diminished proportion of regulatory T cells (Tregs). Mesenchymal stem cells (MSCs) have been shown to modulate immune responses by de novo induction and expansion of Tregs. In this study, we analyzed the molecular and cellular mechanisms involved in Treg-associated pregnancy protection following MSCs administration in an abortion-prone mouse mating. In a case-control study, syngeneic abdominal fat-derived MSCs were administered intraperitoneally (i.p) to the DBA/2-mated CBA/J female mice on day 4.5 of pregnancy. Abortion rate, Tregs proportion in spleen and inguinal lymph
Objective: Multiple myeloma (MM) is an incurable plasma cell malignancy. Several genetic and epigenetic changes affect numerous critical genes expression status in this disorder. CDKN2A gene is expressed at low level in almost all cases with MM disease. The mechanism of this gene down-regulation has remained controversial. In the present study, we targeted EZH2 by microRNA-124 (miR-124) in L-363 cells and assessed following possible impact on CDKN2A gene expression and phenotypic changes.Materials and Methods: In this experimental study, growth inhibitory effects of miR-124 were measured by MTT assay in L-363 cell line. Likewise, cell cycle assay was measured by flowcytometery. The expression levels of EZH2 and CDKN2A were evaluated by real
Natural killer cells, which play a pivotal role in the establishment and maintenance of normal pregnancy, are the most abundant leukocytes at the fetomaternal interface that their subsets frequencies and cytokine profile are influential factors in the preservation of the decidual tolerogenic microenvironment. Any imbalance in NK cells' frequency and functions could be associated with pregnancy failure. Mesenchymal stem cells (MSCs) are shown to have immunomodulatory effects on NK cells and their cytokine profile. The purpose of this study is to evaluate the impact of MSCs therapy on the cytokine profiles and subpopulations of NK cells in a murine model of recurrent pregnancy loss. Adipose-derived MSCs were injected intraperitoneally to the
Matrix metalloproteinases-(MMP)-9 facilitates the migration of T-cells to central nervous system (CNS), while (Tissue Inhibitor of Metalloproteinases-1) TIMP-1 inhibits the function of MMP-9. This study aimed to determine the appropriate treatment option for multiple sclerosis (MS). Forty-three relapsing-remitting MS (RRMS) patients were randomly divided into two groups of 22 (group A, placebo) and 21 (group B, Saffron pill) individuals. Serum samples were collected from patients’ blood before using the Saffron pills/placebo pills and then after 12 months. The serum level of MMP-9 and its inhibitor, as well as TIMP-1, were measured by ELISA kits. Data were analysed using SPSS version 13. MMP-9 serum levels noticeably decreased in patients
Natural killer cells, which play a pivotal role in the establishment and maintenance of normal pregnancy, are the most abundant leukocytes at the fetomaternal interface that their subsets frequencies and cytokine profile are influential factors in the preservation of the decidual tolerogenic microenvironment. Any imbalance in NK cells' frequency and functions could be associated with pregnancy failure. Mesenchymal stem cells (MSCs) are shown to have immunomodulatory effects on NK cells and their cytokine profile. The purpose of this study is to evaluate the impact of MSCs therapy on the cytokine profiles and subpopulations of NK cells in a murine model of recurrent pregnancy loss. Adipose‐derived MSCs were injected intraperitoneally to t
Abstract Objective: Dendritic cells (DCs) as major regulators of the immune response in the decidua play a pivotal role in establishment and maintenance of pregnancy. Immunological disorders are considered to be the main causes of unexplained recurrent spontaneous abortions (RSAs). Recently, we reported that mesenchymal stem cells (MSCs) therapy could improve fetal survival and reduce the abortion rate in abortion-prone mice, although the precise mechanisms of this action are poorly understood. Since MSCs have been shown to exert immunomodulatory effects on the immune cells, especially DCs, this study was performed to investigate the capability of MSCs to modulate the frequency, maturation state, and phenotype of uterine DCs (uDCs) as a pot
Objective: Dendritic cells (DCs) are professional antigen presenting cells majorly modulated by various environmental factors. Leukemia inhibitory factor (LIF) is a pleiotropic cytokine from interleukin-6 family. Previous studies demonstrate that LIF is associated with several tolerogenic events; yet the exact effect of this cytokine on the generation and function of DCs was not explicitly identified.Materials and methods: To clarify the role of LIF in DCs development, immature DCs were differentiated from mouse bone marrow (BM) in a GM-CSF and IL-4 containing medium with or without LIF. Afterwards, in maturation process, the differentiated DCs were exposed to TNF-α in the presence or absence of LIF.Results: Immature DCs differentiated in
ObjectiveMesenchymal stem cells (MSCs), due to their immunomodulatory functions, are an ideal candidate for the treatment of immune-related diseases. Recurrent spontaneous abortion (RSA) is one of the most common complications of pregnancy which in many cases is related to the immune system disorders. Our previous study has shown that the abortion rate was decreased following the syngeneic MSCs therapy in abortion-prone mice. In this study, the therapeutic effect of syngeneic, allogeneic, and xenogeneic MSCs was compared in a mouse model of RSA.Materials and MethodsIn this experimental study, MSCs were isolated from adipose tissue (ASCs) of CBA/J and BALB/c mice and human. After characterization, ASCs were injected (IP) at day 4 of gestatio
Nowadays, due to a growing number of tissue injuries, in particular, skin wounds, induction and promotion of tissue healing responses can be considered as a crucial step towards a complete regeneration. Recently, biomaterial design has been oriented towards promoting a powerful, effective, and successful healing. Biomaterials with wound management abilities have been developed for different applications such as providing a native microenvironment and supportive matrices that induce the growth of tissue, creating physical obstacles against microbial contamination, and to be used as delivery systems for therapeutic reagents. Until now, numerous strategies aiming to accelerate the wound healing process have been utilized and stu
Application of “bioactive materials”, as a modified version of biomaterials, can optimize the response of the biological system due to their surface reactivity and formation of strong interactions with the adjacent tissue upon implantation. However, choosing an appropriate bioactive material that suits to the application and provides the desired mechanical, physical, chemical and biological functionality, as well as understanding the aspects of biological reaction to the biomaterial, in particular immune response, it plays a key role in successful integration of the implant. In this review, we will discuss different bioactive materials including bioactive ceramics, polymers and composites and their applications in drug de
Tumor microenvironment interacts with tumor cells, establishing an atmosphere to contribute or suppress the tumor development. Among the cells which play a role in the tumor microenvironment, mesenchymal stem cells (MSCs) have been demonstrated to possess the ability to orchestrate the fate of tumor cell, drawing the attentions to the field. MSCs have been considered as cells with double-bladed effects, implicating either tumorigenic or anti-tumor activity. On the other side, the promising potential of MSCs in treating human cancer cells has been observed from the clinical studies. Among the beneficial characteristics of MSCs are the natural tumor-trophic migration ability, providing facility for drug delivery and, therefore, targeted treat