Monitoring Cell Activation and Extracellular Vesicle Generation in Platelet Concentrates for Transfusion.

Platelets play a crucial role in blood transfusions, and understanding the changes that occur during their storage is important for maintaining the quality of preparations. In this study, we examined key alternating factors, with a particular focus on platelet activation and the release of extracellular vesicles. Additionally, we compared two detection methods-imaging flow cytometry (IFC) and nanoparticle tracking analysis (NTA)-for their effectiveness in detecting particles.

The most frequent HLA alleles around the world: A fundamental synopsis.

A comprehensive knowledge of human leukocyte antigen (HLA) molecular variation worldwide is essential in human population genetics research and disease association studies and is also indispensable for clinical applications such as allogeneic hematopoietic cell transplantation, where ensuring HLA compatibility between donors and recipients is paramount. Enormous progress has been made in this field thanks to several decades of HLA population studies allowing the development of helpful databases and bioinformatics tools. However, it is still difficult to appraise the global HLA population diversity in a synthetic way.

Post-radiation xerostomia therapy with allogeneic mesenchymal stromal stem cells in patients with head and neck cancer: study protocol for phase I clinical trial.

Background: Xerostomia is a common side effect of radiotherapy in patients with head and neck tumors that negatively affects quality of life. There is no known effective standard treatment for xerostomia. Here, we present the study protocol used to evaluate the safety and preliminary efficacy of allogeneic mesenchymal stromal stem cells (MSCs) derived from umbilical cord tissue.

Intraoperative Intradermal Application of Stromal Vascular Fraction into the Abdominal Suture Line: Histological Analysis of Abdominal Scar Tissue.

Background: Stem cell therapy is a promising new approach to wound healing. Stromal vascular fraction is a heterogeneous collection of cells, including adipose-derived stem cells, which are traditionally isolated using a manual collagenase-based technique. To our knowledge, this is the first human study that histologically assesses the potential of intraoperative intradermal injection of stromal vascular fraction on skin regeneration.

Combined TLR-3/TLR-8 Signaling in the Presence of α-Type-1 Cytokines Represents a Novel and Potent Dendritic Cell Type-1, Anti-Cancer Maturation Protocol.

During the ex vivo generation of anti-cancer dendritic cell (DC)-based vaccines, their maturation still represents one of the most crucial steps of the manufacturing process. A superior DC vaccine should: possess extensive expression of co-stimulatory molecules, have an exceptional type-1 polarization capacity characterized by their ability to produce IL-12p70 upon contact with responding T cells, migrate efficiently toward chemokine receptor 7 (CCR7) ligands, and have a superior capacity to activate cytotoxic T cell responses. A major advance has been achieved with the discovery of the next generation maturation protocol involving TLR-3 agonist (poly I:C), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)-γ, and IFN-α, and has since been known as α-type-1 maturation cocktail.

Mixed cultures of allogeneic dendritic cells are phenotypically and functionally stable - a potential for primary cell-based "off the shelf" product generation.

Vaccination against tumors using antigen-pulsed dendritic cell (DC) vaccines has greatly evolved over the last decade, with hundreds of active human clinical trials well on the way. The use of an autologous source for DC-based vaccine therapeutics remains the obvious choice in the majority of clinical studies; however, novel evidence suggests that an allogeneic source of DCs can yield success if administered in the right context. One of the challenges facing successful DC vaccination protocols is the generation of large enough numbers of DCs intended for vaccination and standardization of these procedures.

Programmed death ligand 1 (PD-L1) plays a vital part in DC tolerogenicity induced by IFN-γ.

Interferon-γ (IFN-γ) is the sole representative of type II IFNs, with well recognized role in numerous inflammatory processes. Lately, its significant pleiotropic nature has been recognized in many scenarios, where IFN-γ contributes to maintenance or induction of tolerogenic responses in context of various immune cell types. In this manuscript we demonstrate, that IFN-γ-mediated induction of programmed death ligand 1 (PD-L1) on human monocyte-derived dendritic cells (DCs) represents an important tolerogenic aspect in immunological network of type II IFNs.

Overview of Cellular Immunotherapies within Transfusion Medicine for the Treatment of Malignant Diseases.

Over the years, transfusion medicine has developed into a broad, multidisciplinary field that covers different clinical patient services such as apheresis technology and the development of stem cell transplantation. Recently, the discipline has found a niche in development and production of advanced therapy medicinal products (ATMPs) for immunotherapy and regenerative medicine purposes. In clinical trials, cell-based immunotherapies have shown encouraging results in the treatment of multiple cancers and autoimmune diseases.

Recent advances on smart glycoconjugate vaccines in infections and cancer.

Vaccination is one of the greatest achievements in biomedical research preventing death and morbidity in many infectious diseases through the induction of pathogen-specific humoral and cellular immune responses. Currently, no effective vaccines are available for pathogens with a highly variable antigenic load, such as the human immunodeficiency virus or to induce cellular T-cell immunity in the fight against cancer. The recent SARS-CoV-2 outbreak has reinforced the relevance of designing smart therapeutic vaccine modalities to ensure public health.

Emerging glyco-based strategies to steer immune responses.

Glycan structures are common posttranslational modifications of proteins, which serve multiple important structural roles (for instance in protein folding), but also are crucial participants in cell-cell communications and in the regulation of immune responses. Through the interaction with glycan-binding receptors, glycans are able to affect the activation status of antigen-presenting cells, leading either to induction of pro-inflammatory responses or to suppression of immunity and instigation of immune tolerance. This unique feature of glycans has attracted the interest and spurred collaborations of glyco-chemists and glyco-immunologists to develop glycan-based tools as potential therapeutic approaches in the fight against diseases such as cancer and autoimmune conditions.

Putting the spotlight on donation-related risks and donor safety - are we succeeding in protecting donors?

Background And Objective: The European consortium project TRANSPOSE (TRANSfusion and transplantation: PrOtection and SElection of donors) aimed to assess and evaluate the risks to donors of Substances of Human Origin (SoHO), and to identify gaps between current donor vigilance systems and perceived risks.

Materials And Methods: National and local data from participating organizations on serious and non-serious adverse reactions in donors were collected from 2014 to 2017. Following this, a survey was performed among participants to identify risks not included in the data sets.

Effects of heterochronic, non-myeloablative bone marrow transplantation on age-related behavioural changes in mice.

Experiments using heterochronic parabionts, i.e. young and old animals connected surgically and hence developing a shared circulation, have shown that blood-borne factors, transferred from young to old mice and vice versa, play a role in influencing a range of health outcomes associated with advanced age.

Recent discoveries in dendritic cell tolerance-inducing pharmacological molecules.

Dendritic cells (DCs) represent one of the most important biological tools for cellular immunotherapy purposes. There are an increasing number of phase I and II studies, where regulatory or tolerogenic DCs (TolDCs) are utilized as negative vaccines, with the aim of inducing tolerogenic outcomes in patients with various autoimmune or chronic-inflammatory diseases, as well as in transplant settings. The induction of tolerogenic properties in DCs can be achieved by altering their activation state toward expression of immunosuppressive elements and/or by achieving resistance to maturation, which leads to insufficient co-stimulatory signal delivery and inability to efficiently present antigens.

Pathogen reduction of blood components during outbreaks of infectious diseases in the European Union: an expert opinion from the European Centre for Disease Prevention and Control consultation meeting.

Pathogen reduction (PR) of selected blood components is a technology that has been adopted in practice in various ways. Although they offer great advantages in improving the safety of the blood supply, these technologies have limitations which hinder their broader use, e.g.

Synergistic Effects of Interferon-γ and Vitamin D Signaling in Induction of ILT-3PDL-1 Tolerogenic Dendritic Cells.

In the past, interferon (IFN)-γ and vitamin D (vit D) have both been associated with induction of tolerogenic characteristics in human dendritic cells (DCs). Although there are only a few reports on interdependency of their actions, the interplay between IFN-γ and vit D has been clearly demonstrated in certain aspects of immune reactivity. Since both agents have been associated with regulation of immune responses, we set out to examine their functional and mechanistic interactions in context of principal regulators of immunity, the DCs.

The use of flow cytometry in the diagnosis of heparin-induced thrombocytopenia (HIT).

Heparin-induced thrombocytopenia (HIT) affects some of the patients exposed to heparin. It is mediated by antibodies that recognize neoepitopes on platelet factor 4 (PF4)/heparin complexes. A HIT diagnosis requires both clinical and laboratory evaluation and remains a challenge.

Dendritic Cells Generated in the Presence of Platelet Lysate Have a Reduced Type 1 Polarization Capacity.

Previously, we have shown platelet lysate (PL) can be used as a non-xenogeneic serum supplement for generation of monocyte-derived dendritic cells (DCs). Since DC-based activation protocols are extremely sensitive to microenvironmental changes such as replacement of culture medium, we wanted to examine the behavior of DCs cultured in the presence of PL under various type-1 activation conditions and assess their type 1 polarization capacity. We compared the quality of DCs cultured in 10% PL-supplemented RPMI medium (plDCs) with clinical-grade DCs obtained using commercially available serum-free medium (sfDCs), frequently used in established DC vaccine protocols.

Dual Role of but Not Inflammasome Polymorphisms in Type 1 Diabetes and Celiac Disease in Children.

Genetic polymorphisms in genes coding for inflammasome components and have been associated with autoinflammatory and autoimmune diseases. On the other hand several studies suggested that NLRP3 inflammasome contributes to maintenance of gastrointestinal immune homeostasis and that activation of NLRP3 is regulated by protein tyrosine phosphatase non-receptor 22 (PTPN22). polymorphism was implicated in the risk for various autoimmune diseases including type 1 diabetes (T1D) but not for celiac disease (CD).

Utility of serological biomarkers for giant cell arteritis in a large cohort of treatment-naïve patients.

Early diagnosis and treatment of giant cell arteritis (GCA) is crucial for preventing ischemic complications. Multiple serological markers have been identified; however, there is a distinct lack of predicting markers for GCA relapse and complications. Our main objective was to identify serological parameters in a large cohort of treatment-naïve GCA patients, which could support clinicians in evaluating the course of the disease.

Insight into structural requirements for selective and/or dual CXCR3 and CXCR4 allosteric modulators.

Based on the previously published pyrazolopyridine-based hit compound for which negative allosteric modulation of both CXCR3 and CXCR4 receptors was disclosed, we designed, synthesized and biologically evaluated a set of novel, not only negative, but also positive allosteric modulators with preserved pyrazolopyridine core. Compound 9e is a dual negative modulator, inhibiting G protein activity of both receptors. For CXCR4 receptor para-substituted aromatic group of compounds distinguishes between negative and positive modulation.

Analysis of Drug Effects on Primary Human Coronary Artery Endothelial Cells Activated by Serum Amyloid A.

Background: RA patients have a higher incidence of cardiovascular diseases compared to the general population. Serum amyloid A (SAA) is an acute-phase protein, upregulated in sera of RA patients.

Aim: To determine the effects of medications on SAA-stimulated human coronary artery endothelial cells (HCAEC).

The level of heparin-induced antibodies in correlation with the result of the flow cytometric functional assay in the patients with suspected HIT.

Heparin can induce the formation of antibodies against a heparin complex with a platelet factor 4 (PF4), leading to platelet activation and the development of heparin-induced thrombocytopaenia (HIT). Because screening ELISA does not discriminate between platelet activating and non-activating anti-heparin/PF4 antibodies, each positive result is confirmed by an additional functional assay. We analysed 1004 sera of patients with suspected HIT.

High-risk genotypes HLA-DR3-DQ2/DR3-DQ2 and DR3-DQ2/DR4-DQ8 in co-occurrence of type 1 diabetes and celiac disease.

Shared susceptibility alleles in the HLA region contribute to the co-existence of type 1 diabetes (T1D) and celiac disease (CD). The aim of our study was to identify HLA genotype variations that influence co-occurrence of T1D and CD (T1D + CD) and the order of their onset. Totally 244 patients, 67 with T1D, 68 with CD and 69 with T1D + CD, (split into "T1D first" and "CD first"), were analyzed.

The European antibody network's practical guide to finding and validating suitable antibodies for research.

Antibodies are widely exploited as research/diagnostic tools and therapeutics. Despite providing exciting research opportunities, the multitude of available antibodies also offers a bewildering array of choice. Importantly, not all companies comply with the highest standards, and thus many reagents fail basic validation tests.

Resolution of HLA-B*44:02:01G, -DRB1*14:01:01G and -DQB1*03:01:01G reveals a high allelic variability among 12 European populations.

Within the framework of the EU-funded HLA-NET action, an analysis of three G-group alleles, HLA-B*44:02:01G, DRB1*14:01:01G and DQB1*03:01:01G, was undertaken in 12 European populations. Ambiguities were resolved by polymerase chain reaction-sequence-specific amplification (PCR-SSP) or PCR-sequence-based typing (PCR-SBT) in a total of 5095 individuals. The results of the DRB1*14:01/14:54 ambiguity showed high relative ratios (24-53%) of DRB1*14:01 in Bulgarians, Croatians, Greeks, Italians and Slovenians, contrasting with low ratios (6-13%) in Austrians, Finnish, French, Hungarians, Norwegians and Swiss.