Abstract In the last 10 years, the role of mesenchymal stromal cells (MSCs) in modulating inflammatory and immune responses has been characterized using both in vitro studies and in vivo models of ...immune disorders. Mesenchymal stromal cell immunomodulatory properties have been linked to various paracrine factors which expression varies depending on the pathologic condition to which the MSCs are exposed. These factors may directly impact key cells of the adaptive immune system, such as T cells. Indeed, coculturing MSCs with T cells in a mixed lymphocyte reaction assay inhibits T-cell proliferation through the secretion of immunomodulatory cytokines. However, in a context of inflammation, MSCs may secrete paracrine factors that influence other immune cell subpopulations such as dendritic cells and macrophages and polarize them toward a tolerogenic phenotype. In vivo, these same immunomodulatory factors are shown to be increased in the serum of animal models presenting with inflammatory diseases treated with MSC administration. In light of the results from these landmark studies, we review the main MSC secreted factors identified to play a role in modulating inflammatory immune responses either in vitro or in vivo , and we assess the impact of these factors on the therapeutic applications of MSC-based cell therapies in immune diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
BACKGROUND
Whole blood (WB) is rapidly emerging as the treatment modality of choice for the initial resuscitation of civilian trauma patients across the United States. The reemergence of WB has been ...rapid and driven in part by recognition of the importance of early plasma transfusion in the resuscitation process.
STUDY DESIGN AND METHODS
The study was designed as a critical analysis of the available literature on WB transfusion in civilian trauma patients. Studies were included if they reported on transfusion of cold‐stored WB used in a civilian setting and measured safety, feasibility, or a direct clinical outcome.
RESULTS
Examination of the available literature supports the feasibility and safety of WB used in treatment of civilian trauma patients. The evidence regarding clinical outcomes, particularly with direct comparison to equivalent doses of component therapy, is more limited. The literature is predominantly descriptive and retrospective in nature and limited by the heterogeneity of clinical WB protocols being used. Based on this limited data set, there are limited conclusions that can be used to definitely support or refute the clinical superiority of WB to component therapy.
CONCLUSION
Current literature supports the safety and feasibility of WB, but prospective randomized trials comparing WB to component therapy are needed to provide the definitive evidence on this topic.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
The success of allogeneic hematopoietic stem cell transplantation is dependent on a world‐wide network of collection centers providing donations that predominantly have been infused as ...fresh cells. The logistics chain that supports the just‐in‐time delivery model for stem cell and immunotherapy products was severely stressed by the COVID pandemic, and in early 2020 a number of national and international bodies recommended that cells should be cryopreserved at the collection or transplant center to avoid interruptions in their acquisition or delivery to patients who had started conditioning.
Study Design
To assess the potential consequences of such pandemic‐related deviations to normal practice, we surveyed nine international laboratories to determine if the characteristics or transplant outcomes of allogeneic stem cell donations differed in the immediate periods before and after the switch to routine cryopreservation.
Results
Nine centers on two continents provided data for 72 HSC donations just before, and 71 just after, switching to cryopreservation for allogeneic HSC products. No statistically significant differences between the period before and after cryopreservation were noted for time from product collection to receipt, product temperature at receipt, or CD34+ cell viability at receipt. There was an indication of slower absolute neutrophil count recovery after cryopreservation was required (mean time of 15 vs. 17.6 days).
Discussion
While there were no apparent changes to most parameters studied, there was an indication of slower neutrophil engraftment that will need to be examined in larger, longer term studies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The complement is a key player of the innate immune response. It provides defense mechanisms that are not specific, but very efficient at neutralizing any invader, accounting for 4% of the proteins ...in the peripheral blood. Nevertheless, there is a dark side to the complement system, as it may activate its machinery against healthy cells such as peripheral blood red blood cells and platelets resulting in undesired hemolysis and thrombocytopenia, respectively. Understanding and identifying the role of complement in these settings allow physicians to adjust their diagnostic and therapeutic modalities accordingly. The role of complement in the pathophysiology and management of autoimmune hemolytic anemia and of alloimmune-mediated thrombocytopenia is under investigation and discussed.
Le système du complément est un élément important de l’immunité innée. Ce système comprend 4 % des protéines circulant dans le sang et procure une défense non spécifique mais immédiate en cas d’agression infectieuse. Ce système efficace est à double tranchant, car il est parfois actif par inadvertance contre des cellules vitales comme les globules rouges et les plaquettes, conduisant à des crises d’hémolyses et de thrombopénies réfractaires. Il est donc primordial d’analyser au mieux le rôle du complément dans ces pathologies sanguines aiguës et parfois réfractaires, pour améliorer leur diagnostic ainsi que la conduite thérapeutique, qui sont décrites ci-jointes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Pancreatic islet encapsulation within biosynthetic materials has had limited clinical success due to loss of islet function and cell death. As an alternative encapsulation material, a ...silk-based scaffold was developed to reestablish the islet microenvironment lost during cell isolation. Islets were encapsulated with ECM proteins (laminin and collagen IV) and mesenchymal stromal cells (MSCs), known to have immunomodulatory properties or to enhance islet cell graft survival and function. After a 7 day in vitro encapsulation, islets remained viable and maintained insulin secretion in response to glucose stimulation. Islets encapsulated with collagen IV, or laminin had increased insulin secretion at day 2 and day 7, respectively. A 3.2-fold synergistic improvement in islet insulin secretion was observed when islets were co-encapsulated with MSCs and ECM proteins. Furthermore, encapsulated islets had increased gene expression of functional genes; insulin I, insulin II, glucagon, somatostatin, and PDX-1, and lower expression of the de-differentiation genes cytokeratin 19 and vimentin compared to non-encapsulated cells. This work demonstrates that encapsulation in silk with both MSCs and ECM proteins enhances islet function and with further development may have potential as a suitable platform for islet delivery in vivo.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
BACKGROUND
The Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial was a randomized clinical trial comparing survival after transfusion of two different blood component ratios ...for emergency resuscitation of traumatic massive hemorrhage. Transfusion services supporting the study were expected to provide thawed plasma, platelets, and red blood cells within 10 minutes of request.
STUDY DESIGN AND METHODS
At the 12 Level 1 trauma centers participating in PROPPR, blood components transfused and delivery times were tabulated, with a focus on universal donor (UD) plasma management. The adequacy of site plans was assessed by comparing the bedside blood availability times to study goals and the new American College of Surgeons guidelines.
RESULTS
Eleven of 12 sites were able to consistently deliver 6 units of thawed UD plasma to their trauma‐receiving unit within 10 minutes and 12 units in 20 minutes. Three sites used blood group A plasma instead of AB for massive transfusion without complications. Approximately 4700 units of plasma were given to the 680 patients enrolled in the trial. No site experienced shortages of AB plasma that limited enrollment. Two of 12 sites reported wastage of thawed AB plasma approaching 25% of AB plasma prepared.
CONCLUSION
Delivering UD plasma to massively hemorrhaging patients was accomplished consistently and rapidly and without excessive wastage in high‐volume trauma centers. The American College of Surgeons Trauma Quality Improvement Program guidelines for massive transfusion protocol UD plasma availability are practicable in large academic trauma centers. Use of group A plasma in trauma resuscitation needs further study.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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