German Red Cross

About: German Red Cross is a healthcare organization based out in Berlin, Germany. It is known for research contribution in the topics: Transplantation & Mesenchymal stem cell. The organization has 653 authors who have published 1146 publications receiving 40111 citations. The organization is also known as: Deutsches Rotes Kreuz & DRK.

Evaluation of the Elecsys Chagas Assay for Detection of Trypanosoma cruzi-Specific Antibodies in a Multicenter Study in Europe and Latin America.

Abstract: Serology is the preferred method to confirm a Chagas disease diagnosis and to screen blood donors. A battery of assays is often required due to the limited accuracy of single assays. The Elecsys Chagas assay is a newly developed, double-antigen sandwich assay for use on the Elecsys and cobas e immunoassay analyzers, intended to identify individuals infected with Trypanosoma cruzi, for diagnosis and screening. The performance of the Elecsys Chagas assay was evaluated in comparison with those of other widely used T. cruzi antibody assays, at multiple sites (Europe/Latin America). Relative sensitivity and specificity were assessed by using samples from blood donors, pregnant women, and hospitalized patients from regions where Chagas disease is endemic and from regions of nonendemicity. The Elecsys Chagas assay had an overall relative sensitivity of 100% (n = 674). Overall relative specificities were 99.90% (n = 14,681), 100% (n = 313), and 100% (n = 517) for samples from blood donors, pregnant women, and hospitalized patients, respectively. The analytical specificity was 99.83% (n = 594). The Elecsys Chagas assay detected T. cruzi antibodies in two World Health Organization (WHO) standard T. cruzi reference panels (panels 09/188 and 09/186) at a 1:512 dilution, corresponding to a cutoff sensitivity of approximately 1 mIU/ml. The Elecsys Chagas assay demonstrated robust performance under routine conditions at multiple sites in Europe and Latin America. In contrast to other available Chagas assays, the Elecsys assay uses a reduced number of recombinant T. cruzi antigens, resulting in a significantly smaller number of cross-reactions and improved analytical specificity while being highly sensitive.

Preserved effector functions of human ORAI1- and STIM1-deficient neutrophils

Abstract: To the Editor: The endoplasmic reticulum (ER) Ca sensor stromal interaction molecule 1 (STIM1) and the plasma membrane protein ORAI1, which forms the pore of the Ca release-activated Ca (CRAC) channel, are the core components of storeoperated calcium entry (SOCE). SOCE is an essential pathway of lymphocyte activation, where engagement of immunostimulatory receptors triggers Ca release from the ER through inositol 1,4,5 trisphosphate formation. STIM1 and STIM2 subsequently induce opening of CRAC channels, which are composed of ORAI proteins (ORAI1-ORAI3). Inherited mutations in ORAI1 or STIM1 genes, which abolish SOCE, cause a combined immunodeficiency syndrome accompanied by various nonhematopoietic manifestations. Whereas the T-cell defect is well established as a key mechanism mediating the immunophenotype of SOCE-deficient patients, the contribution of dysfunctional innate immunity to the broad susceptibility to infections in affected patients is unclear. In particular, data on human polymorphonuclear neutrophils (PMNs) derived from SOCE-deficient patients are lacking. Studies in mice and in human neutrophil-like cell lines suggest a substantial role for SOCE in antimicrobial PMN functions, including phagocytosis, degranulation, and superoxide (reactive oxygen species [ROS]) production. In contrast, other reports implicate non-SOCE mechanisms, such as receptor-operated Ca entry, which is directly mediated by cell-surface receptors and independent of ER stores, as important mediators of PMN activation. A more detailed understanding of SOCE in PMN function is of obvious importance both for understanding the susceptibility to the broad spectrum of microorganisms in patients with SOCE deficiency and because SOCE inhibition in PMNs has been proposed as an anti-inflammatory treatment strategy. We analyzed Ca signals and effector functions in PMNs from 2 patients with loss-of-function mutations in ORAI1 and STIM1 genes. Surprisingly, and in contrast to T cells, Ca influx was only mildly reduced in ORAI1and STIM1-deficient PMNs, and detailed studies did not reveal overt defects in PMN function. Accordingly, in contrast to mice, STIM1 and ORAI1 do not appear to be critical for various effector functions of human PMNs. Methodically, human PMNs were isolated from EDTA blood by means of Biocoll (Biochrom, Berlin, Germany) density gradient centrifugation. Intracellular Ca mobilization was measured by using flow cytometry after labeling with Indo-1 (Invitrogen, Grand Island, NY) and stimulation with formylated methionyl-leucyl-phenylalanine (fMLP; 100 mmol/L), heatfixed streptococci (10/mL), ionomycin (2 mmol/L), or thapsigargin (1 mmol/L). The functional PMN assays (adhesion, chemotaxis, IL-8 production, and ROS formation) were described earlier. Phagocytosis of fluorophore-stained and heat-fixed streptococci was measured by means of flow cytometry after PMN fixation with paraformaldehyde and trypan blue quenching. More details are provided in the Methods section and Table E1 in this article’s Online Repository at www.jacionline.org.

Recent advances in understanding mesenchymal stromal cells.

Abstract: Mesenchymal stromal cells (MSCs) are among of the most studied cell type for cellular therapy thanks to the ease of isolation, cultivation, and the high ex vivo expansion potential. In 2018, the European Medicines Agency finally granted the first marketing authorization for an MSC product. Despite the numerous promising results in preclinical studies, translation into routine practice still lags behind: therapeutic benefits of MSCs are not as satisfactory in clinical trial settings as they appear to be in preclinical models. The bench-to-bedside-and-back approach and careful evaluation of discrepancies between preclinical and clinical results have provided valuable insights into critical components of MSC manufacturing, their mechanisms of action, and how to evaluate and quality-control them. We sum up these past developments in the introductory section ("Mesenchymal stromal cells: name follows function"). From the huge amount of information, we then selected a few examples to illustrate challenges and opportunities to improve MSCs for clinical purposes. These include tissue origin of MSCs, MSC culture conditions, immune compatibility, and route of application and dosing. Finally, we add some information on MSC mechanisms of action and translation into potency assays and give an outlook on future perspectives raising the question of whether the future clinical product may be cell-based or cell-derived.

Autologous Mesenchymal Stroma Cells Are Superior to Allogeneic Ones in Bone Defect Regeneration

Abstract: The application of autologous mesenchymal stem cells (MSC) for the treatment of bone defects requires two invasive procedures and several weeks of ex vivo cell expansion. To overcome these limitations, the administration of allogeneic MSC may be attractive, because they are anticipated to be immunoprivileged. Because preclinical studies using various animal models are conflicting with respect to the efficacy of allogeneic MSC, we investigated whether autologous and allogeneic human MSC (hMSC) are equally effective in regenerating bone in a humanized mouse model resembling the human immune system. Applying autologous and allogeneic hMSC in critically sized femoral defects, we found that allogeneic hMSC elicited a mild immune response early after implantation, whereas early angiogenic processes were similar in both treatments. At later healing time points, the transplantation of allogeneic hMSC resulted in less bone formation than autologous hMSC, associated with a reduced expression of the osteogenic factor Runx2 and impaired angiogenesis. We found by species-specific staining for collagen-type-1α2 that MSCs of either source did not synthesize new bone matrix, indicating an indirect contribution of transplanted hMSC to bone regeneration. In conclusion, our data suggest that the application of autologous hMSC is superior to that of allogeneic cells for bone defect treatment.