Engineered extracellular vesicles expressing ICAM-1: A promising targeted delivery system for T cell modifications.

Background: Extracellular vesicles (EVs) are natural nano-carriers that possess the required crucial features of an ideal biomolecular delivery system. However, using unmodified EVs may have some limitations such as low accumulation in target sites. Studies have established that engineering EVs against different cell surface markers can overcome most of these hurdles.

Fluorescence labeling of anchor-modified Mart-1 peptide for increasing its affinity for HLA-A*0201: Hit two targets with one arrow.

One of the most successful strategies in designing peptide-based cancer vaccines is modifying natural epitope peptides to increase their binding strength to human leukocyte antigens (HLAs). Anchor-modified Mart-1 peptide (ELAGIGILTV) is among the artificial epitope peptides with the highest binding affinity for HLA-A*0201. In this study, by fluorescence labeling of its either C- or N-terminus with N -(5-carboxyfluorescein)-l-lysine, we not only made it traceable but also drastically increased its binding strength to HLA-A*0201.

The Effect of Age and Cell Culture Parameters on the Quantity and Function of Bone Marrow-derived Dendritic Cells.

Dendritic cells (DCs) are a group of bone marrow-derived cells that play a crucial role in innate and acquired immune responses. Bone marrow-derived dendritic cells (BMDC) are used in many studies, so the efficiency and purity of the differentiated cells are essential. This study aimed to investigate the effect of several parameters, including the age of mice, cell culture medium, and swirling of the culture plate, to increase the efficiency of the induced cells, considering the standard protocols.

Inhibition of apelin/APJ axis enhances the potential of dendritic cell-based vaccination to modulate TH1 and TH2 cell-related immune responses in an animal model of metastatic breast cancer.

Purpose: The immunosuppressive microenvironment of tumors reduces the effectiveness of immunotherapies. Apelin as an immunosuppressor peptide is expressed in the microenvironment of many tumors. Thus, inhibition of apelin-related protumor activities can promote the effectiveness of cancer immunotherapy.

Mesenchymal stem cell therapy attenuates complement C3 deposition and improves the delicate equilibrium between angiogenic and anti-angiogenic factors in abortion-prone mice.

Immunological disorders are one of the main causes of recurrent spontaneous abortions (RSA). A rapidly expanding body of evidence indicates that excessive activation of the complement system is critically involved in the development of miscarriages. In the CBA/J × DBA/2 murine model of recurrent miscarriage, exaggerated and unrestrained complement activation is reported to be the underlying cause of angiogenic factor imbalance and persistent inflammation.

Simultaneous transduction of dendritic cells with A20 and BTLA genes stimulates the development of stable and efficient tolerogenic dendritic cells and induces regulatory T cells.

Background: This study investigated the potential of simultaneous overexpression of A20 and B- and T-lymphocyte attenuator (BTLA) genes in dendritic cells (DCs) to develop a tolerogenic phenotype in DCs and investigate their capabilities for induction of immunosuppression.

Methods: Plasmid vectors were designed harboring A20, BTLA, and A20 + BTLA genes and were transfected to HEK 293T cells to produce lentiviruses. DCs were transduced by the gene carrying viruses and evaluated for the surface expression of MHCII, CD40, and CD86 molecules by flow-cytometry.

Recombinant CD137-Fc, its synthesis, and applications for improving the immune system functions, such as tumor immunotherapy and to reduce the inflammation due to the novel coronavirus.

CD137 (ILA/4-1BB), a member of tumor necrosis factor receptor superfamily, is one of the most important T cell costimulatory molecules. Interaction of this molecule with its ligand transmits a two-way signal that activates both T lymphocyte and antigen presenting cells. The soluble form of CD137 (sCD137) reduces the activity of its membrane isoform and is associated with T lymphocyte activation-induced cell death.

Mesenchymal stem cells induce expansion of regulatory T cells in abortion-prone mice.

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 the 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.

A Randomized, Triple-blind Placebo-controlled Trial to Determine the Effect of Saffron on the Serum Levels of MMP-9 and TIMP-1 in Patients with Multiple Sclerosis.

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.

Mesenchymal stem cells alter the frequency and cytokine profile of natural killer cells in abortion-prone mice.

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.

New Insights Into Implementation of Mesenchymal Stem Cells in Cancer Therapy: Prospects for Anti-angiogenesis Treatment.

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 cells, drawing the attention to the field. MSCs have been considered as cells with double-bladed effects, implicating either tumorigenic or anti-tumor activity.

Uterine Dendritic Cells Modulation by Mesenchymal Stem Cells Provides A Protective Microenvironment at The Feto-Maternal Interface: Improved Pregnancy Outcome in Abortion-Prone Mice.

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.

Leukemia inhibitory factor (LIF) modulates the development of dendritic cells in a dual manner.

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.

Comparison of The Therapeutic Effect of Syngeneic, Allogeneic, and Xenogeneic Adipose Tissue-Derived Mesenchymal Stem Cells on Abortion Rates in A Mouse Model.

Objective: Mesenchymal 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.

Engineered Exosomes for Targeted Transfer of siRNA to HER2 Positive Breast Cancer Cells.

Exosomes are the best options for gene targeting, because of their natural, nontoxic, non-immunogenic, biodegradable, and targetable properties. By engineering exosome-producing cells, ligands can be expressed fusing with exosomal surface proteins for targeting cancer cell receptors. In the present study, HER2-positive breast cancer cells were targeted with a modified exosome producing engineered HEK293T cell.

Mesenchymal stem cells therapy protects fetuses from resorption and induces Th2 type cytokines profile in abortion prone mouse model.

The imbalance of Th1/Th2 cytokines is well known in recurrent spontaneous abortion (RSA) mouse model. Mesenchymal stem cells (MSCs) possess potent immunoregulatory properties that could modulate the Th1 cytokine responses in benefit of Th2 types. In this study, we aimed to analyze the local and systemic balance of Th1/Th2 cytokines following MSCs therapy.

CD40 Knocked Down Tolerogenic Dendritic Cells Decrease Diabetic Injury.

Background: Type-1 diabetes (T1D) is an autoimmune disease in which T lymphocytes destroy insulin-producing β-cells. Control of self-reactive T lymphocytes and recovery of diabetic injury is the end point of T1D.

Objective: To investigate generation of tolerogenic dendritic cells (tolDCs) as an innovative method of diabetes therapy.

Mesenchymal Stem Cell Therapy Prevents Abortion in CBA/J × DBA/2 Mating.

Immunological disorders are among the main causes of recurrent spontaneous abortions (RSAs). Mesenchymal stem cells (MSCs) have been shown to modulate various aspects of immune responses. It seems that MSCs may improve the immunological conditions in immune-mediated RSA.

In silico designing, cloning, and heterologous expression of novel chimeric human B lymphocyte CD20 extra loop.

Design and production of monoclonal antibody for the diagnosis and immunotherapy of non-Hodgkin lymphoma require a suitable CD20 antigen as an effective immunogen. In this study, a new chimeric human CD20 extra loop (hCD20EXL) protein was designed by bioinformatics tools and was expressed in Escherichia coli BL21 DE3. Amino acid sequences, protein structure, immunogenicity, and other physicochemical property of potential antigens were in silico analyzed.

Conjugated Alpha-Alumina nanoparticle with vasoactive intestinal peptide as a Nano-drug in treatment of allergic asthma in mice.

Asthma is a chronic respiratory disease characterized by airway inflammation, bronchoconstriction, airway hyperresponsiveness and recurring attacks of impaired breathing. Vasoactive intestinal peptide (VIP) has been proposed as a novel anti-asthma drug due to its effects on airway smooth muscle relaxation, bronchodilation and vasodilation along with its immunomodulatory and anti-inflammatory properties. In the current study, we investigated the therapeutic effects of VIP when conjugated with α-alumina nanoparticle (α-AN) to prevent enzymatic degradation of VIP in the respiratory tract.

Is TGFβ as an anti-inflammatory cytokine required for differentiation of inflammatory T17 cells?

T-Helper 17 (T17) cells are a CD4 T subset that plays a critical role in the pathophysiology of inflammatory disorders, especially chronic forms. It seems that the derivation of T17 cells from their precursors take place in inflammatory microenvironment. The role of transforming growth factor (TGF)-β as an anti-inflammatory cytokine in T17 cell differentiation is controversial.

Role of cytomegalovirus on the maturation and function of monocyte derived dendritic cells of liver transplant patients.

Aim: To study the impact of association between cytomegalovirus (CMV) pathogenesis with dendritic cell (DC) maturation and function was evaluated in CMV reactivated liver transplanted patients in comparing with non-reactivated ones, and healthy controls.

Methods: Monocyte derived dendritic cells (MoDCs) was generated from collected ethylenediaminetetraacetic acid-treated blood samples from patient groups and controls. In these groups, expression rates and mean fluorescent intensity of DC markers were evaluated using flowcytometry technique.

The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells.

Mesenchymal stem cells (MSCs), as cells with potential clinical utilities, have demonstrated preferential incorporation into inflammation sites. Immunophenotype and immunomodulatory functions of MSCs could alter by inflamed-microenvironments due to the local pro-inflammatory cytokine milieu. A major cellular mediator with specific function in promoting inflammation and pathogenicity of autoimmunity are IL-17-producing T helper 17 (Th17) cells that polarize in inflamed sites in the presence of pro-inflammatory cytokines such as Interleukin-1β (IL-1β), IL-6 and IL-23.

A novel dendritic cell-targeted lentiviral vector, encoding Ag85A-ESAT6 fusion gene of Mycobacterium tuberculosis, could elicit potent cell-mediated immune responses in mice.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), leading to high mortality worldwide. It is well-established that cellular immunity plays a critical role to control Mtb infection. Dendritic Cells (DCs) are potent antigen presenting cells, which play an important role to prime cell-mediated immune responses.

Decidual soluble factors, through modulation of dendritic cells functions, determine the immune response patterns at the feto-maternal interface.

Dendritic cells (DCs) can acquire immunogenic or tolerogenic properties depending on intrinsic and tissue environmental factors. We aimed to determine the immunomodulatory effects of decidual soluble factors from abortion- and non-abortion-prone mice on DC functions. The decidual cell supernatants (DS) were obtained from abortion-prone and non-abortion-prone mice.