Background The rapid clinical translation of mesenchymal stem cells (MSC) has resulted in the development of cell-based strategies for multiple indications. Unfortunately one major barrier to widespread implementation of MSC-based therapies is the limited supply of fetal calf serum (FCS) used to expand cells to therapeutic numbers. Additionally, the xenogeneic element of fetal calf serum has been previously demonstrated to stimulate antibody mediated reactions and in some cases sensitization leading to anaphylaxis. Method XcytePLUS™ media, a human platelet lysate based product, was used to supplement the culture medium at 5, 7.5 and 10% and compared to fetal calf serum at 10%, for human umbilical cord MSC expansion. Properties of the expanded cells were investigated. Results This study demonstrated equivalent or superior effects of human platelet lysate compared to standard FCS supplemented media, based on doubling rate, without loss of identity or function, as demonstrated with flow cytometry characterization. Differentiation into osteocytes, adipocytes and chondrocytes was comparable from cells expanded in either media supplement. Conclusions These data support the implementation of human platelet lysate supplemented media as an alternative to xenogeneic containing preparations which may lead to safer MSC products with therapeutic uses.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by the progressive erosion of the synovial membrane, destruction of cartilage, bone erosion, and, ultimately, the loss of joint functionality. Additionally, RA may exhibit various systemic effects that can cause severe disability. Although the introduction of biological disease-modifying antirheumatic drugs (DMARDs) has revolutionized the standard of care, a substantial proportion of the population do not achieve significant responses or develop resistance. Additionally, patients that do respond to DMARDs can have numerous adverse effects as well as limited ability to regenerate lost tissue. Here, we discuss the immunology of RA, how mesenchymal stem cells (MSCs) block the pathology of RA, and we provide an overview of animal and clinical studies supporting the use of MSCs in the treatment of RA. We also describe preliminary data using our proprietary pluripotent derived MSCs (pMSC) that can be utilized for induction of antigen-specific tolerance.

Advancing personalized medicine in brain cancer relies on innovative strategies, with mRNA vaccines emerging as a promising avenue. While the initial use of mRNA vaccines was in oncology, their stunning success in COVID-19 resulted in widespread attention, both positive and negative. Regardless of politically biased opinions, which relate more to the antigenic source than form of delivery, we feel it is important to objectively review this modality as relates to brain cancer. This class of vaccines trigger robust immune responses through MHC-I and MHC-II pathways, in both prophylactic and therapeutic settings. The mRNA platform offers advantages of rapid development, high potency, cost-effectiveness, and safety. This review provides an overview of mRNA vaccine delivery technologies, tumor antigen identification, combination therapies, and recent therapeutic outcomes, with a particular focus on brain cancer. Combinatorial approaches are vital to maximizing mRNA cancer vaccine efficacy, with ongoing clinical trials exploring combinations with adjuvants and checkpoint inhibitors and even adoptive cell therapy. Efficient delivery, neoantigen identification, preclinical studies, and clinical trial results are highlighted, underscoring mRNA vaccines' potential in advancing personalized medicine for brain cancer. Synergistic combinatorial therapies play a crucial role, emphasizing the need for continued research and collaboration in this area.

The COVID-19 pandemic has posed significant therapeutic challenges in addressing acute respiratory distress syndrome (ARDS). This serious illness has caused numerous fatalities worldwide and has had profound health and economic impacts. Previous studies have shown that mesenchymal stem cells (MSCs) can suppress ARDS. In this case series, we report on the treatment of nine patients with a single intravenous dose of 100 million hypoxic cultured umbilical cord-derived MSCs (UC-MSCs). Following the intravenous administration of UC-MSCs, obtained from the lining of the umbilical cord, longitudinal laboratory analysis revealed a sustained decrease in inflammatory markers and stabilized pulmonary function in eight out of nine patients. UC-MSCs possess immunomodulatory and anti-inflammatory properties, enabling them to attenuate the cytokine storm and potentially aid in lung repair. Importantly, no adverse events associated with the treatment were observed. These findings collectively suggest that a cell-based approach significantly enhances the survival rate of ARDS induced by SARS-CoV-2 and offers a promising treatment option in both preclinical and clinical settings.

Background : Chronic lower back pain caused by degenerative disc disease (DDD) is a significant cause of morbidity and mortality, which is currently treated by surgical means such as fusion, or mechanical means such as artificial discs.Only a minority of patients with DDD are eligible for these procedures and in numerous cases they require re-intervention.Cell therapy has been utilized for many spine-based procedures with mixed results.Our goal was to evaluate cell therapy in the treatment of non-surgical DDD.Aim : To perform a pilot study using autologous bone marrow aspirate for treatment of non-surgical, chronic lower back pain.Methods : In this prospective, observational cohort study, fifteen patients between 18 and 85 years of age with the diagnosis of non-surgical chronic lower back pain were enrolled to receive paraspinal injections of autologous bone marrow aspirate.In order to qualify, patients must have been diagnosed with degenerative disease in one, two, or three lumbar discs with predominant back pain after having failed conservative treatment including optimized physical therapy for over 6 months.Patients with surgical back pain as determined by a neuro-specialist, spinal deformity, or spinal instability were all disqualified from participating.All enrolled patients underwent outpatient bone marrow aspiration using the Marrow Cellutions kit.The aspirate was then injected into the paraspinal area using image guidance via ultrasound with each patient having an average of six injections.The patients were then followed at 30, 60, 90, 180, 360, and 720 days.The Oswestry Disability Index and Visual Analogue Scale were used to objectively assess for any change in the patient's mobility and back pain post procedure.Results : Fourteen of the fifteen patients had injections near the L4, L5, and/or S1 region bilaterally.Evaluation of patients at 1, 30, 90, 180, 360, and 720 days revealed significant improvement in mobility using the Oswestry Disability Index and reduction in pain score using the Visual Analogue Scale.The mean pain score changed from 8.9 at baseline to 4.3 at 30 days and sustained to 1.8 at 6 months, 1.3 at 12 months and 2.2 at 24 months with a gradual reduction in overall pain medication utilization guided by their healthcare team.Two patients at the 24-month time point had recurrence of symptoms without significant MRI changes, and opted to be treated with medical therapy.They both had pain scores back up to 5 and an Oswestry score of 30 and 32 respectively.There was some short-term bruising in two patients at the harvest site and no long-term adverse events were reported related to the procedure.Overall, the procedure was safely performed on 15/15 patients (100%) and 13/15 patients (87%) still had durable results at two years.Conclusion : This data supports the further investigation of paraspinal administration of non-manipulated autologous bone marrow aspirate for reducing pain and improving mobility in patients with non-surgical lower back pain.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12967-021-02852-z

The Editor-in-Chief and the publisher have retracted this article [1]. An investigation by the Lithuanian Bioethics Committee concluded that, contrary to the statements in the article, the study described was not conducted in the Vilnius City Clinical Hospital and the Commission of Medical Ethics did not issue any approval for such a study.

Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), is growing at an exponential rate worldwide. Manifestations of this disease are heterogeneous; however, advanced cases often exhibit various acute respiratory distress syndrome-like symptoms, systemic inflammatory reactions, coagulopathy, and organ involvements. A common theme in advanced COVID-19 is unrestrained immune activation, classically referred to as a "cytokine storm", as well as deficiencies in immune regulatory mechanisms such as T regulatory cells. While mesenchymal stem cells (MSCs) themselves are objects of cytokine regulation, they can secrete cytokines to modulate immune cells by inducing anti-inflammatory regulatory Treg cells, macrophages and neutrophils; and by reducing the activation of T and B cells, dendritic and nature killer cells. Consequently, they have therapeutic potential for treating severe cases of COVID-19. Here we discuss the unique ability of MSCs, to act as a "living anti-inflammatory", which can "rebalance" the cytokine/immune responses to restore equilibrium. We also discuss current MSC trials and present different concepts for optimization of MSC therapy in patients with COVID-19 acute respiratory distress syndrome.

The immune modulatory potential of mesenchymal stem cells (MSCs) is well known and is the basis for multiple clinical trials in treatment of autoimmune conditions. Unfortunately, MSCs are relatively rare, difficult to expand in culture, and methods of obtaining MSCs are complicated and expensive. In contrast, fibroblasts are found in copious amounts in various tissues, are a robust cellular population, and can be cultured without need for costs associated with culture media. Previous studies by our group and others have demonstrated fibroblasts possess regenerative activities. In the current study we demonstrated: a) fibroblasts inhibit mixed lymphocyte reaction; b) suppress T cell activation; c) inhibit DC maturation; and d) stimulate T regulatory (Treg) cell formation. Importantly, administration of fibroblasts in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis resulted in disease inhibition, which was abrogated upon depletion of Treg cells. This data, combined with existing clinical safety data on fibroblast administration, supports the clinical translation of fibroblast-based therapies for multiple sclerosis.

This study examined the quality of bone marrow aspirates extracted using a novel, FDA cleared method to optimally target cells from the inner cortical iliac bone surface without the need for centrifugation. This method employs small draws from a single puncture that promote only lateral flow from multiple sites (SSLM method). The study utilized the Marrow Cellutions bone marrow aspiration system (MC system) which is based on the SSLM method and compared the MC system directly to bone marrow concentrates (BMAC) generated by centrifugation of aspirates harvested with a standard aspiration needle.

Disclosed are methods, compositions of matter, and protocols useful for the detection of altered cells in a patient. Immune cells capable of clonal expansion are engineered to produce a soluble signal upon activation and/or clonal expansion. The cells may possess a suicide gene, inducible upon administration pharmacological or light/radiation activatable, so as to eliminate the cells from body when desired. In another embodiment, immune cells produce a localized marker, the marker being visible with imaging technology. In other embodiments cells capable of non-clonal expansion are utilized. The disclosure provides means of utilizing the immunosurveillance properties of immune cells to diagnose and localize diseases associated with alteration of host cells.

Disclosed are methods of preventing pregnancy through induction of immunological responses through vaccination with placental extracts and products associated with placentation. In one particular embodiment an immune response is triggered towards pregnancy associated neoangiogenesis through administration of placental endothelial cells capable of triggering immunity. In other embodiments the process of replicating immunological events associated with pregnancy failure are recapitulated by stimulation of immunity to antigens such as VEGFR-1, VEGFR-2, CD105, FGF1-R, Integrin αvβ3, and CD-248.

Background: Xenon (Xe) is a noble gas that has been used for the last several decades as an anesthetic during surgery. Its antagonistic effect on glutamate subtype of NMDA (N-methyl-D-aspartate) receptors resulted in evaluation of this gas for treatment of CNS pathologies, including psychoemotional disorders. The aim of this study was to assess the behavioral effects of acute inhalation of subanesthetic concentrations of Xe and to study the outcomes of Xe exposure in valproic acid (VPA)-induced rodent model of autism. Methods: We have conducted two series of experiments with a battery of behavioral tests aimed to evaluate locomotion, anxiety- and depression-like behavior, and social behavior in healthy, VPA-treated and Xe-exposed young rats. Results: We have shown that in healthy animals Xe exposure resulted in acute and delayed decrease of exploratory motivation, partial decrease in risk-taking and depressive-like behavior as well as improved sensorimotor integration during the negative geotaxis test. Acute inhalations of Xe in VPA-exposed animals led to improvement in social behavior, decrease in exploratory motivation, and normalization of behavior in forced-swim test. Conclusion: Behavioral modulatory effects of Xe are probably related to its generalized action on excitatory/inhibitory balance within the CNS. Our data suggest that subanesthetic short-term exposures to Xe have beneficial effect on several behavioral modalities and deserves further investigation.

Diabetic foot ulcers are associated with significant morbidity and mortality, and current treatments are far from optimal. Chronic wounds in diabetes are characterised by impaired angiogenesis, leukocyte function, fibroblast proliferation, and keratinocyte migration and proliferation. Methods: We tested the effect of exposure to argon gas on endothelial cell, fibroblast, macrophage and keratinocyte cell cultures in vitro and in vivo of a streptozotocin-induced diabetic mouse model. Results: Exposure to normobaric argon gas promotes multiple steps of the wound healing process. Argon accelerated angiogenesis, associated with upregulation of pro-angiogenic Angiopoietin-1 and vascular endothelial growth factor (VEGF) signalling in vitro and in vivo. Treatment with argon enhanced expression of transforming growth factor (TGF)-β, early recruitment of macrophages and keratinocyte proliferation. Argon had a pro-survival effect, inducing expression of cytoprotective mediators B-cell lymphoma 2 and heme oxygenase 1. Argon was able to accelerate wound closure in a diabetic mouse model. Conclusion: Together these findings indicate that argon gas may be a promising candidate for clinical use in treatment of diabetic ulcers.

Tumor necrosis factor (TNF)-alpha was originally identified in the 1970s as the serum mediator of innate immunity capable of inducing hemorrhagic necrosis in tumors. Today, a wide spectrum of biological activities have been attributed to this molecule, and clinical translation has mainly occurred not in using it to treat cancer, but rather to inhibit its effects to treat autoimmunity. Clinical trials utilizing systemic TNF-alpha administration have resulted in an unacceptable level of toxicities, which blocked its development. In contrast, localized administration of TNF-alpha in the form of isolated limb perfusion have yielded excellent results in soft tissue sarcomas. Here we describe a novel approach to leveraging the potent antineoplastic activities of TNF-alpha by enhancing activity of locally produced TNF-alpha through extracorporeal removal of soluble TNF-alpha receptors. Specifically, it is known that cancerous tissues are infiltrated with monocytes, T cells, and other cells capable of producing TNF-alpha. It is also known that tumors, as well as cells in the tumor microenvironment produce soluble TNF-alpha receptors. The authors believe that by selectively removing soluble TNF-alpha receptors local enhancement of endogenous TNF-alpha activity may provide for enhanced tumor cell death without associated systemic toxicities.

INTRODUCTION: The tumor cells could escape from the immune elimination through the immunoediting mechanisms including the generation of immunosuppressive or immunoregulative cells. By contrast, allograft transplantation could activate the immune system and induce a strong allogenic response. The aim of this study was to investigate the efficacy of allogenic skin transplantation in the inhibition of tumor growth through the activation of allogenic immune response. METHODS: Full-thickness skin transplantation was performed from C57BL/6 (H-2b) donors to BALB/c (H-2d) recipients that were receiving subcutaneous injection of isogenic CT26 colon cancer cells (2 × 106 cells) at the same time. The tumor size and pathological changes, cell populations and cytokine profiles were evaluated at day 14 post-transplantation. RESULTS: The results showed that as compared to non-transplant group, the allogenic immune response in the skin-grafting group inhibited the growth of tumors, which was significantly associated with increased numbers of intra-tumor infiltrating lymphocytes, increased populations of CD11c+MHC-classII+CD86+ DCs, CD3+CD4+ T cells, CD3+CD8+ T cells, and CD19+ B cells, as well as decreased percentage of CD4+CD25+Foxp3+ T cells in the spleens. In addition, the levels of serum IgM and IgG, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were significantly higher within the tumor in skin transplant groups than that in non-transplant group. CONCLUSIONS: Allogenic skin transplantation suppresses the tumor growth through activating the allogenic immune response, and it may provide a new immunotherapy option for the clinical refractory tumor treatment.