Mesenchymal stem cell-based therapy as a new therapeutic approach for acute inflammation.

Acute inflammatory diseases such as acute colitis, kidney injury, liver failure, lung injury, myocardial infarction, pancreatitis, septic shock, and spinal cord injury are significant causes of death worldwide. Despite advances in the understanding of its pathophysiology, there are many restrictions in the treatment of these diseases, and new therapeutic approaches are required. Mesenchymal stem cell-based therapy due to immunomodulatory and regenerative properties is a promising candidate for acute inflammatory disease management. Based on preclinical results, mesenchymal stem cells and their-derived secretome improved immunological and clinical parameters. Furthermore, many clinical trials of acute kidney, liver, lung, myocardial, and spinal cord injury have yielded promising results. In this review, we try to provide a comprehensive view of mesenchymal stem cell-based therapy in acute inflammatory diseases as a new treatment approach.

COVID-19 immunotherapy: Treatment based on the immune cell-mediated approaches.

Multiple efforts are currently underway to control and treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19) worldwide. Despite all efforts, the virus that emerged in Wuhan city has rapidly spread globally and led to a public health emergency of international concern (PHEIC) due to the lack of approved antiviral therapy. Nevertheless, SARS-CoV-2 has had a significant influence on the evolution of cellular therapeutic approaches. Adoptive immune cell therapy is innovative and offers either promising prophylactic or therapy for patients with moderate-to-severe COVID-19. This approach is aimed at developing safety and providing secure and effective therapy in combination with standard therapy for all COVID-19 infected individuals. Based on the effective results of previous studies on both inflammatory and autoimmune diseases, various immune cell therapies against COVID-19 have been reviewed and discussed. It must be considered that the application of cell therapy for treatment and to eliminate infected respiratory cells could result in excessive inflammation, so this treatment must be used in combination with other treatments, despite its many beneficial efforts.

Adipose-Derived Mesenchymal Stem Cells and Conditioned Medium Attenuate the Memory Retrieval Impairment During Sepsis in Rats.

In this study, we hypothesized that sepsis induction impairs memory retrieval in rats while transplanted mesenchymal stem cells (MSCs) and MSC-conditioned medium (MSC-CM) application are capable of attenuating those complications. MSCs were obtained from adipose tissue of rats and at the second culture passage; MSCs and MSC-CM were collected. Rats were randomly divided into four experimental groups: sham, CLP, MSC, and MSC-CM. Sepsis was induced by cecal ligation and puncture (CLP) model in the CLP, MSC, and MSC-CM groups. The MSC group received 1 × 106 MSCs/rat (i.p., 2 h after CLP surgery); the MSC-CM rats received the conditioned medium (CM) from 1 × 106 MSCs intraperitoneally 2 h after sepsis induction. Novel object recognition test, sepsis score, and blood pressure measurement were performed 24 h after the treatments. The right hippocampus was taken for western blot analysis. CLP rats showed a significantly higher sepsis score and systolic blood pressure. They also had a significant increase in the phosphorylated form of CAMKII-α, cleaved caspase 3 and Bax/Bcl2 ratio, and a reduction in c-fos protein in the hippocampus tissue samples compared with the sham group. MSC transplantation and MSC-CM administration significantly decreased the mean sepsis score and prevented sepsis-induced attenuation of blood pressure compared with the CLP rats. Animals in the MSC and MSC-CM groups showed a better memory retrieval, attenuation in phosphorylated form of CAMKII-α, cleaved caspase 3 and Bax/Bcl2 ratio, and an increase in c-fos protein expression compared with the CLP group. It seems that CAMKII and c-fos are inversely involved in regulating memory processes in hippocampus. Phosphorylated form of CaMKII-α overexpression may impair the ability of object recognition. Our findings confirmed that MSC-CM application has more advantages compared with transplanted MSCs and may be offered as a promising therapy for inflammatory diseases such as severe sepsis.

Hydrogen Peroxide Preconditioning Promotes Protective Effects of Umbilical Cord Vein Mesenchymal Stem Cells in Experimental Pulmonary Fibrosis.

Purpose: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disorder with few available treatments. Mesenchymal stem cell therapy (MSCT), an innovative approach, has high therapeutic potential when used to treat IPF. According to recent data, preconditioning of MSCs can improve their therapeutic effects. Our research focuses on investigating the anti-inflammatory and antifibrotic effects of H2 O2 -preconditioned MSCs (p-MSCs) on mice with bleomycin-induced pulmonary fibrosis (PF). Methods: Eight-week-old male C57BL/6 mice were induced with PF by intratracheal (IT) instillation of bleomycin (4 U/kg). Human umbilical cord vein-derived MSCs (hUCV-MSCs) were isolated and exposed to a sub-lethal concentration (15 µM for 24 h) of H2 O2 in vitro. One week following the injection of bleomycin, 2×105 MSCs or p-MSCs were injected (IT) into the experimental PF. The survival rate and weight of mice were recorded, and 14 days after MSCs injection, all mice were sacrificed. Lung tissue was removed from these mice to examine the myeloperoxidase (MPO) activity, histopathological changes (hematoxylin-eosin and Masson's trichrome) and expression of transforming growth factor beta 1 (TGF-ß1) and alpha-smooth muscle actin (α-SMA) through immunohistochemistry (IHC) staining. Results: Compared to the PF+MSC group, p-MSCs transplantation results in significantly decreased connective tissue (P<0.05) and collagen deposition. Additionally, it is determined that lung tissue in the PF+pMSC group has increased alveolar space (P<0.05) and diminished expression of TGF-ß1 and α-SMA. Conclusion: The results demonstrate that MSCT using p-MSCs decreases inflammatory and fibrotic factors in bleomycin-induced PF, while also able to increase the therapeutic potency of MSCT in IPF.

Ankylosing spondylitis and mesenchymal stromal/stem cell therapy: a new therapeutic approach.

Ankylosing spondylitis (AS) is an inflammatory rheumatoid disease categorized within spondyloarthropathies (SpA) and manifested by chronic spinal arthritis. Several innate and adaptive immune cells and secreted-mediators have been indicated to play a role in AS pathogenesis. Considering the limitations of current therapeutic approaches (NSAIDs, glucocorticoids, DMARDs and biologic drugs), finding new treatments with fewer side effects and high therapeutic potentials are required in AS. Mesenchymal stem cells (MSCs) with considerable immunomodulatory and regenerative properties could be able to attenuate the inflammatory responses and help tissue repair by cell-to-cell contact and secretion of soluble factors. Moreover, MSCs do not express HLA-DR, which renders them a favorable therapeutic choice for transplantation in immune-mediated disorders. In the present review, we describe immunopathogenesis and current treatments restrictions of AS. Afterwards, immunomodulatory properties and applications of MSCs in immune-mediated disorders, as well as recent findings of clinical trials involving mesenchymal stem cell therapy (MSCT) in ankylosing spondylitis, will be discussed in detail. Additional studies are required to investigate several features of MSCT such as cell origin, dosage, administration route and, specifically, the most suitable stage of disease for ideal intervention.

Immunomodulatory Effects of Blood Transfusion on Tumor Size, Metastasis, and Survival in Experimental Fibrosarcoma.

In spite of efforts, blood transfusion is still accompanied with adverse effects such as transfusion-related immunomodulation (TRIM). The current study aimed to evaluate the effects of allogeneic, syngeneic, fresh and storage blood transfusion on the growth and metastasis of tumors and survival in fibrosarcoma bearing BALB/c mice. Twenty-five BALB/c mice were grouped into five groups of equal size. All groups were injected 1.2 × 106 WEHI-164 cells subcutaneously to induce fibrosarcoma tumor. After expansion of the tumor, in four groups (except for the control group), hemorrhage-induced anemia was developed. Twenty-four hours later, blood deficit was replaced by fresh allogeneic, storage allogeneic, fresh syngeneic and storage syngeneic blood transfusion, respectively. After a blood transfusion, for 13 days, the tumor size and survival of the mice were evaluated. In the day 20, the mice were sacrificed and their spleen tissues were evaluated for TRIM induced metastasis. Tumor size increase in the groups that received allogeneic (fresh and storage) and storage syngeneic blood transfusion was significantly higher than the control group (P value < 0.05). However, no significant difference was present in survival between the experiment groups and the control group. There was no metastasis in none of groups at the end of the study. Allogeneic and storage blood transfusion could have immunomodulatory effects such as increased tumor size. However, it seems that fresh and syngeneic blood transfusion have no effects on tumor growth in fibrosarcoma bearing mice. Further evidence may prove that more attention is warranted in blood transfusion into cancer cases.

Immune cells involved in the pathogenesis of ankylosing spondylitis.

Ankylosing spondylitis (AS) is an inflammatory autoimmune disease. AS is a prototype form of spondyloarthropathies (SpA). The precise etiology of AS has not been fully understood. But Inflammation has a critical role in the pathogenesis of the disease. The immune system by various cells, secreted-mediators and markers manage and regulate the immune responses and inflammation. Every factor which disturbed this regulation and hemostasis can cause chronic inflammation. In this review, we discussed the role of several innate and adaptive immune cells involved in the triggering, initiation, development, and regulation of AS.