Systems biology of stored blood cells: can it help to extend the expiration date?

Efst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinnWith increasingly stringent regulations regarding deferral and elimination of blood donors it will become increasingly important to extend the expiration date of blood components beyond the current allowed storage periods. One reason for the storage time limit for blood components is that platelets and red blood cells develop a condition called storage lesions during their storage in plastic blood containers. Systems biology provides comprehensive bio-chemical descriptions of organisms through quantitative measurements and data integration in mathematical models. The biological knowledge for a target organism can be translated in a mathematical format and used to compute physiological properties. The use of systems biology represents a concrete solution in the study of blood cell storage lesions, and it may open up new avenues towards developing better storage methods and better storage media, thereby extending the storage period of blood components. This article is part of a Special Issue entitled: Integrated omics.info:eu-repo/grantAgreement/EC/FP7/23281

Solution casting of chitosan membranes for in vitro evaluation of bioactivity.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Considerable research is focusing on the surface modification of titanium implants for the treatment of orthopaedic tissue injuries to increase the success of orthopaedic fixations. Chitosan is one of the natural materials under investigation based on several favourable properties. Numerous techniques have been described for the preparation of chitosan membranes, including solution casting methods for the investigation of bioactivity before applying coatings onto potential titanium implants. Solution casting enables the easy in-house evaluation of chitosan membranes and allows for the selection of promising chitosan materials.We present a method for the standardized and easily applied preparation of chitosan membranes by solution casting. This protocol is suitable for chitosan materials spanning a wide degree of deacetylation, being derived from different chitin sources and chitosan derivatives with novel properties. We detail the preparation and quality control methods in order to prepare membranes with favourable bioactivity, sustaining cell attachment and proliferation for extended culture periods.The possibilities associated with the use of chitosan in tissue engineering applications are far from being exhausted and numerous challenges remain prior to successful translation into the clinics. Based on our experience, we have developed simple in-house methods for quality control of homogeneous membrane casting and early prediction of successful experimental outcome.Icelandic Research Fund 090007023 Icelandic Technology Development Fund 06136200

Herding cats: managing gold atoms on common transparent dielectrics

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadSimple methods to control the self-organization of gold atoms on commonly employed transparent dielectrics are presented. On one hand, surface diffusion of gold atoms can be suppressed to a sufficient degree as to realize ultra-thin (as low as approximately 5 nm) void-free semi-transparent conducting gold films over macroscopic areas while, on the other hand, their high surface mobility can be harnessed to fabricate large-area substrates compatible with cell culturing and imaging, having widely tunable field-enhancement properties for surface-enhanced Raman scattering.Icelandic Research Fun

Current transfusion practice and need for new blood products to ensure blood supply for patients with major hemorrhage in Europe

Background: New blood products are considered for treatment of patients with major hemorrhage. The aim of this report is to describe the current transfusion practices in Europe for patients with major hemorrhage and explore the need for new or modified blood products to ensure prehospital and in-hospital blood supply. Study Design and Method: The European Blood Alliance (EBA) Working Group on Innovation and New Blood Products' subgroup on major hemorrhage performed a survey among the EBA member states. Results: The response rate was 58% (17 responses from 15 of the 26 EBA member states). Of these, sixteen (94%) provide massive transfusion packages (MTPs) with balanced ratio of red blood cells and plasma. Seven of the respondents included platelets from the start of treatment. Eleven (65%) provide prehospital blood products, mainly red cell concentrates or dried and/or thawed plasma with 5 days of extended storage. Two countries provide prehospital whole blood. Twelve respondents (71%) saw a need for implementation of new or modified blood components in their institution. The top three priorities were whole blood (12 of 12, 100%), dried plasma (8 of 12, 67%), and cold-stored platelets (7 of 12, 58%). Discussion: Current national guidelines for use of blood products in patients with major hemorrhage in Europe agree on the use of balanced transfusion, however the timing and source of platelets differ. Blood products for prehospital transfusion are available in several European countries. An interest in new or modified blood products for patients with major hemorrhage was observed, especially for whole blood.publishedVersio

POGZ Is Required for Silencing Mouse Embryonic β-like Hemoglobin and Human Fetal Hemoglobin Expression

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesFetal globin genes are transcriptionally silenced during embryogenesis through hemoglobin switching. Strategies to derepress fetal globin expression in the adult could alleviate symptoms in sickle cell disease and β-thalassemia. We identified a zinc-finger protein, pogo transposable element with zinc-finger domain (POGZ), expressed in hematopoietic progenitor cells. Targeted deletion of Pogz in adult hematopoietic cells in vivo results in persistence of embryonic β-like globin expression without affecting erythroid development. POGZ binds to the Bcl11a promoter and erythroid-specific intragenic regulatory regions. Pogz+/- mice show elevated embryonic β-like globin expression, suggesting that partial reduction of Pogz expression results in persistence of embryonic β-like globin expression. Knockdown of POGZ in primary human CD34+ progenitor cell-derived erythroblasts reduces BCL11A expression, a known repressor of embryonic β-like globin expression, and increases fetal hemoglobin expression. These findings are significant, since new therapeutic targets and strategies are needed to treat β-globin disorders.Frederick National Laboratory for Cancer Research, NIH intramural research program of the NHLBI, NIH intramural research program of the NIDDK, NIH USUH

Current status and future prospects of genome-scale metabolic modeling to optimize the use of mesenchymal stem cells in regenerative medicine and biomaterials

Mesenchymal stem cells are a promising source for externally grown tissue replacements and patient-specific immunomodulatory treatments. This promise has not yet been fulfilled in part due to production scaling issues and the need to maintain the correct phenotype after reimplantation. One aspect of extracorporeal growth that may be manipulated to optimize cell growth and differentiation is metabolism. The metabolism of MSCs changes during and in response to differentiation and immunomodulatory changes. MSC metabolism may be linked to functional differences but how this occurs and influences MSC function remains unclear. Understanding how MSC metabolism relates to cell function is however important as metabolite availability and environmental circumstances in the body may affect the success of implantation. Genome-scale constraint based metabolic modelling can be used as a tool to fill gaps in knowledge of MSC metabolism, acting as a framework to integrate and understand various data types (e.g., genomic, transcriptomic and metabolomic). These approaches have long been used to optimize the growth and productivity of bacterial production systems and are being increasingly used to provide insights into human health research. Production of tissue for implantation using MSCs requires both optimized production of cell mass and the understanding of the patient and phenotype specific metabolic situation. This review considers the current knowledge of MSC metabolism and how it may be optimized along with the current and future uses of genome scale constraint based metabolic modelling to further this aim

The Effect of Recombinant Human Interleukin-6 on Osteogenic Differentiation and YKL-40 Expression in Human, Bone Marrow-Derived Mesenchymal Stem Cells.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageHuman mesenchymal stem cells are an attractive cell source for tissue engineering and regenerative medicine applications, especially because of their differentiation potential toward the mesenchymal lineage. Furthermore, this cell type participates in the regeneration of tissue damage and plays an important role in immunity. Similarly, chitinase-like proteins have been proposed to aid in tissue remodeling, inflammation, and differentiation processes. The chitinase-like protein YKL-40 in particular is indicated in preventing damage to the extracellular matrix in response to proinflammatory cytokines, even though its biological function remains speculative. Finally, interleukin (IL)-6, a pleiotropic acute phase protein, participates in the regulation of bone turnover and immunoregulation. The physiological role of IL-6 in bone homeostasis is complex, exerting different effects on osteoblasts and osteoclasts depending on their differentiation stage. The aim of this study was to determine the effect of recombinant human IL-6 (5 ng/mL) on YKL-40 expression and osteogenic differentiation of human mesenchymal stem cells. Recombinant human IL-6 induced a donor-dependent change in mineralization and significantly promoted YKL-40 protein secretion. However, YKL-40 gene expression remained unaffected, and no statistically significant differences in the expression of osteogenic marker genes could be observed

SERS Imaging of Mesenchymal Stromal Cell Differentiation

To access publisher's full text version of this article click on the hyperlink belowUnderstanding the process of mesenchymal stromal cell (MSC) osteogenic differentiation is essential for a wide range of medical applications. However, these primary cells vary significantly from donor to donor, making it difficult to fully exploit their therapeutic potential. Although osteogenic differentiation has been studied extensively, there is still a shortage of standardized methods for the evaluation of the degree of differentiation. Here, we employ noninvasive surface-enhanced Raman scattering (SERS) for studying such cells, offering a better understanding of cellular processes in situ. We present the long-term differentiation of MSCs on biocompatible gold nanoisland SERS substrates, combining imaging of cells with spectroscopic detection of molecular species and chemical events occurring on the cellular membrane adjacent to the surface of the SERS substrate. We detect multiple signs of bone tissue formation, from an early stage to mature osteoblasts, without labeling. We show that the results correlate very well with classical differentiation-detecting assays, indicating that the SERS imaging technique alone is sufficient to study the progress of osteogenic differentiation of such cells, paving a way toward continuous label-free screening of live cells. © 2021 American Chemical Society. Author keywords extracellular matrix; hydroxyapatite; mesenchymal stromal cells; osteogenic differentiation; SERS substrates; stem cells; surface-enhanced Raman scattering (SERS)University of Iceland Research Fund Landspitali University Hospital Research fun

Chitosan leads to downregulation of YKL-40 and inflammasome activation in human macrophages.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageChitosan, the deacetylated derivative of chitin, is used as biomaterial in diverse settings. It is also found on pathogens and can be proinflammatory. Shorter derivatives of chitosan can be generated chemically or enzymatically, chitosan oligosaccharides (ChOS). There is variation in the chemical composition of ChOS, including size distribution, but in general, they have been described as inert or anti-inflammatory. Active human chitinases can cleave chitin and chitosan, while inactive chitinases bind both but do not cleave. Both active and inactive chitinases have important roles in the immune response. The inactive chitinase YKL-40 is expressed highly during inflammation and has been proposed as a marker of poor prognosis. YKL-40 acts as a negative regulator of the inflammasome and as a positive regulator of angiogenesis. Levels of YKL-40 can therefore regulate levels of inflammation, the extent of angiogenesis, and the process of inflammation resolution. This study shows that chitosan leads to reduced secretion of YKL-40 by primary human macrophages and that this is concomitant with inflammasome activation. This was most pronounced with a highly deacetylated ChOS. No effect on the secretion of the active chitinase Chit-1 was detected. Smaller and more acetylated ChOS did not affect YKL-40 levels nor inflammasome activation. We conclude that this effect on the levels of YKL-40 is a part of the proinflammatory mechanisms of chitosan and its derivatives. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 2778-2785, 2015.Landspitali University Hospital Research Fund Icelandic Student Innovation Fund 132341009