Intraperitoneal injection of mesenchymal stem cells-conditioned media (MSCS-CM) treated monocyte can potentially alleviate motor defects in experimental autoimmune encephalomyelitis female mice; An original experimental study.

INTRODUCTION: Multiple sclerosis (MS), as a destructive pathology of myelin in central nervous system (CNS), causes physical and mental complications. Experimental autoimmune encephalomyelitis (EAE) is laboratory model of MS widely used for CNS-associated inflammatory researches. Cell therapy using macrophage M2 (MPM2) is a cell type with anti-inflammatory characteristics for all inflammatory-based neuropathies. This experimental study investigated the probable therapeutic anti-inflammatory effects of intraperitoneal (IP) injection of MPM2 on alleviation of motor defect in EAE-affected animals. MATERIALS AND METHODS: 24 C57/BL6 female mice were divided into four groups of EAE, EAE + Dexa, EAE + PBS, and EAE + MP2. EAE was induced through deep cervical injection of spinal homogenate of guinea pigs. MPM2 cells were harvested from bone marrow and injected (106cells/ml) in three days of 10, 13 and 16 post-immunizations (p.i). Clinical score (CS), anti-inflammatory cytokines (IL-4, IL-10), pro-inflammatory gene expression (TNF-α, IL-1ß) and histopathological investigations (HE, Nissl and Luxol Fast Blue) were considered. Data were analyzed using SPSS software (v.19) and p < 0.05 was considered significant level. RESULTS: During EAE induction, the mean animal weight was decreased (p < 0.05); besides, following MPM2 injection, the weight gain was applied (p < 0.05) in EAE + MPM2 groups than control. Increased (p < 0.05) levels of CS was found during EAE induction in days 17-28 in EAE animals; besides, CS was decreased (p < 0.05) in EAE + MPM2 group than EAE animals. Also, in days 25-28 of experiment, the CS was decreased (p < 0.05) in EAE + MPM2 than EAE + Dexa. Histopathological assessments revealed low density of cell nuclei in corpus callosum, microscopically. LFB staining also showed considerable decrease in white matter density of corpus callosum in EAE group. Acceleration of white matter density was found in EAE + MPM2 group following cell therapy procedure. Genes expression of TNF-α, IL-1ß along with IL-4 and IL-10 were decreased (p < 0.05) in EAE + MPM2 group. CONCLUSION: IP injection of MPM2 to EAE-affected female mice can potentially reduce the CNS inflammation, neuronal death and myelin destruction. MPM2 cell therapy can improve animal motor defects.

Revolutionizing cancer treatment: the power of bi- and tri-specific T-cell engagers in oncolytic virotherapy.

Bi- or tri-specific T cell engagers (BiTE or TriTE) are recombinant bispecific proteins designed to stimulate T-cell immunity directly, bypassing antigen presentation by antigen-presenting cells (APCs). However, these molecules suffer from limitations such as short biological half-life and poor residence time in the tumor microenvironment (TME). Fortunately, these challenges can be overcome when combined with OVs. Various strategies have been developed, such as encoding secretory BiTEs within OV vectors, resulting in improved targeting and activation of T cells, secretion of key cytokines, and bystander killing of tumor cells. Additionally, oncolytic viruses armed with BiTEs have shown promising outcomes in enhancing major histocompatibility complex I antigen (MHC-I) presentation, T-cell proliferation, activation, and cytotoxicity against tumor cells. These combined approaches address tumor heterogeneity, drug delivery, and T-cell infiltration, offering a comprehensive and effective solution. This review article aims to provide a comprehensive overview of Bi- or TriTEs and OVs as promising therapeutic approaches in the field of cancer treatment. We summarize the cutting-edge advancements in oncolytic virotherapy immune-related genetic engineering, focusing on the innovative combination of BiTE or TriTE with OVs.

MiR-320a upregulation contributes to the effectiveness of pemetrexed by inhibiting the growth and invasion of human lung cancer cell line (Calu-6).

BACKGROUND: Lung cancer is a common and deadly disease. Chemotherapy is the most common treatment, which inhibits cancer cell growth. Pemetrexed (PMX) is often used with other drugs. Environmental stress can affect regulatory non-coding RNAs such as MicroRNAs that modify gene expression. This study investigates the effect of PMX on the hsa-miR-320a-3p expression in the Calu-6 lung cancer cell line. METHODS AND RESULT: Calu-6 cells were cultured in an incubator with 37 °C, 5% CO2, and 98% humidity. The MTT test was performed to determine the concentration of PMX required to inhibit 50% of cell growth. To examine growth inhibition and apoptosis, release of lactate dehydrogenase (LDH), cell assays and caspase 3 and 7 enzyme activity were used. Finally, molecular studies were conducted to compare the expression of hsa-miR-320a-3p and genes including VDAC1, DHFR, STAT3, BAX and BCL2 before and after therapy. RESULTS: According to a study, it has been observed that PMX therapy significantly increases LDH release after 24 h. The study found that PMX's IC50 on Calu-6 is 8.870 µM. In addition, the treated sample showed higher expression of hsa-miR-320a-3p and BAX, while the expression of VDAC1, STAT3, DHFR and BCL2 decreased compared to the control sample. CONCLUSION: According to the findings of the current research, hsa-miR-320a-3p seems to have the potential to play an important role in the development of novel approaches to the treatment of lung cancer.

Antiproliferative effects of mesenchymal stem cells carrying Newcastle disease virus and Lactobacillus Casei extract on CT26 Cell line: synergistic effects in cancer therapy.

BACKGROUND AND AIMS: Colorectal Cancer (CRC) is a frequent malignancy with a high mortality rate. Specific inherited and environmental influences can affect CRC. Oncolytic viruses and bacteria in treating CRC are one of the innovative therapeutic options. This study aims to determine whether mesenchymal stem cells (MSCs) infected with the Newcastle Disease Virus (NDV) in combination with Lactobacillus casei extract (L. casei) have a synergistic effects on CRC cell line growth. MATERIALS AND METHODS: MSCs taken from the bone marrow of BALB/c mice and were infected with the 20 MOI of NDV. Then, using the CT26 cell line in various groups as a single and combined treatment, the anticancer potential of MSCs containing the NDV and L. casei extract was examined. The evaluations considered the CT26 survival and the rate at which LDH, ROS, and levels of caspases eight and nine were produced following various treatments. RESULTS: NDV, MSCs-NDV, and L. casei in alone or combined treatment significantly increased apoptosis percent, LDH, and ROS production compared with the control group (P˂0.05). Also, NDV, in free or capsulated in MSCs, had anticancer effects, but in capsulated form, it had a delay compared with free NDV. The findings proved that L. casei primarily stimulates the extrinsic pathway, while NDV therapy promotes apoptosis through the activation of both intrinsic and extrinsic apoptosis pathways. CONCLUSIONS: The results suggest that MSCs carrying oncolytic NDV in combination with L. casei extract as a potentially effective strategy for cancer immunotherapy by promoting the generation of LDH, ROS, and apoptosis in the microenvironment of the CT26 cell line.

Stem cells as an ideal carrier for gene therapy: A new approach to the treatment of hepatitis C virus.

BACKGROUND AND AIM: Various chemical drugs have been approved for the treatment of patients with hepatitis C, but most of these treatments are costly, and also have an inadequate response and many side effects. Also, there is no effective vaccine for hepatitis C due to its high genetic diversity. In recent decades, clinical trials have grown dramatically regarding the benefits of stem cell therapy as a modulator of immune system responses and anti-inflammatory drugs. The most promising point in stem cell therapy and similar therapies is that patients with chronic pain and severe injuries are offered drug-free treatment or surgery. In the present study, we examine the various dimensions of the use of stem cells with the approach of gene therapy carriers as a new treatment method in the treatment of Hepatitis C. METHODS: Search terms were including gene carrier, stem cell therapy, gene therapy, liver disorders, hepatitis C virus. At first, 1000 article titles related to the mentioned keywords for different diseases were found. After removing duplicate titles and items that did not match the scope of the research, articles that met the criteria for entering the research and had usable information were selected. All abstracts of selected articles were studied by researchers. In the initial review, articles related to the title were identified and categorized based on the type of challenge. CONCLUSION: Gene therapy, either directly and in vivo or indirectly and in vitro, requires carriers (vectors) to transfer the gene. These carriers are divided into two groups, viral and non-viral. In indirect gene therapy, living cells are isolated from a person's body and genetically modified. Stem cells have the properties to transfer the desired genes to the patient's body, including the ability to proliferate for a long time and differentiate into the tissue cells in which they are located.

Combination therapy with CAR T cells and oncolytic viruses: a new era in cancer immunotherapy.

Chimeric antigen receptor (CAR) T-cell therapy is an encouraging and fast-growing platform used for the treatment of various types of tumors in human body. Despite the recent success of CAR T-cell therapy in hematologic malignancies, especially in B-cell lymphoma and acute lymphoblastic leukemia, the application of this treatment approach in solid tumors faced several obstacles resulted from the heterogeneous expression of antigens as well as the induction of immunosuppressive tumor microenvironment. Oncolytic virotherapy (OV) is a new cancer treatment modality by the use of competent or genetically engineered viruses to replicate in tumor cells selectively. OVs represent potential candidates to synergize the current setbacks of CAR T-cell application in solid tumors and then and overcome them. As well, the application of OVs gives researches the ability to engineer the virus with payloads in the way that it selectively deliver a specific therapeutic agents in tumor milieu to reinforce the cytotoxic activity of CAR T cells. Herein, we made a comprehensive review on the outcomes resulted from the combination of CAR T-cell immunotherapy and oncolytic virotherapy for the treatment of solid cancers. In the current study, we also provided brief details on some challenges that remained in this field and attempted to shed a little light on the future perspectives.