Human Mesenchymal Stem Cells Protect Human Islets from Pro-Inflammatory Cytokines

Transplantation of human islets is an attractive alternative to daily insulin injections for patients with type 1 diabetes. However, the majority of islet recipients lose graft function within five years. Inflammation is a primary contributor to graft loss, and inhibiting pro-inflammatory cytokine activity can reverse inflammation mediated dysfunction of islet grafts. As mesenchymal stem cells (MSCs) possess numerous immunoregulatory properties, we hypothesized that MSCs could protect human islets from pro-inflammatory cytokines. Five hundred human islets were co-cultured with 0.5 or 1.0×106 human MSCs derived from bone marrow or pancreas for 24 hours followed by 48 hour exposure to interferon-γ, tumor necrosis factor-α and interleukin 1β. Controls include islets cultured alone (± cytokines) and with human dermal fibroblasts (± cytokines). For all conditions, glucose stimulated insulin secretion (GSIS), total islet cellular insulin content, islet β cell apoptosis, and potential cytoprotective factors secreted in the culture media were determined. Cytokine exposure disrupted human islet GSIS based on stimulation index and percentage insulin secretion. Conversely, culture with 1.0×106 bMSCs preserved GSIS from cytokine treated islets. Protective effects were not observed with fibroblasts, indicating that preservation of human islet GSIS after exposure to pro-inflammatory cytokines is MSC dependent. Islet β cell apoptosis was observed in the presence of cytokines; however, culture of bMSCs with islets prevented β cell apoptosis after cytokine treatment. Hepatocyte growth factor (HGF) as well as matrix metalloproteinases 2 and 9 were also identified as putative secreted cytoprotective factors; however, other secreted factors likely play a role in protection. This study, therefore, demonstrates that MSCs may be beneficial for islet engraftment by promoting cell survival and reduced inflammation

Influence of microenvironment on engraftment of transplanted β-cells

Pancreatic islet transplantation into the liver provides a possibility to treat selected patients with brittle type 1 diabetes mellitus. However, massive early β-cell death increases the number of islets needed to restore glucose homeostasis. Moreover, late dysfunction and death contribute to the poor long-term results of islet transplantation on insulin independence. Studies in recent years have identified early and late challenges for transplanted pancreatic islets, including an instant blood-mediated inflammatory reaction when exposing human islets to the blood microenvironment in the portal vein and the low oxygenated milieu of islets transplanted into the liver. Poor revascularization of remaining intact islets combined with severe changes in the gene expression of islets transplanted into the liver contributes to late dysfunction. Strategies to overcome these hurdles have been developed, and some of these interventions are now even tested in clinical trials providing a hope to improve results in clinical islet transplantation. In parallel, experimental and clinical studies have, based on the identified problems with the liver site, evaluated the possibility of change of implantation organ in order to improve the results. Site-specific differences clearly exist in the engraftment of transplanted islets, and a more thorough characterization of alternative locations is needed. New strategies with modifications of islet microenvironment with cells and growth factors adhered to the islet surface or in a surrounding matrix could be designed to intervene with site-specific hurdles and provide possibilities to improve future results of islet transplantation

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Eccentric and isometric shoulder rotator cuff strength testing using a hand-held dynamometer: reference values for overhead athletes

In order to provide science-based guidelines for injury prevention or return to play, regular measurement of isometric and eccentric internal (IR) and external (ER) rotator strength is warranted in overhead athletes. However, up to date, no normative database exists regarding these values, when measured with a hand-held dynamometer. Therefore, the purpose of the study was to provide a normative database on isometric and eccentric rotator cuff (RC) strength values in a sample of overhead athletes, and to discuss gender, age and sports differences. A HHD was used to measure RC strength in 201 overhead athletes between 18 and 50 years old from three different sports disciplines: tennis, volleyball and handball. Isometric as well as eccentric strength was measured in different shoulder positions. Outcome variables of interest were isometric ER and IR strength, eccentric ER strength, and intermuscular strength ratios ER/IR. Our results show significant side, gender and sports discipline differences in the isometric and eccentric RC strength. However, when normalized to body weight, gender differences often are absent. In general, strength differences are in favour of the dominant side, the male athletes and handball. Intermuscular ER/IR ratios showed gender, sports, and side differences. This normative database is necessary to help the clinician in the evaluation of RC strength in healthy and injured overhead athletes. In view of the preventive screening and return-to-play decisions in overhead athletes, normalization to body weight and calculating intermuscular ratios are key points in this evaluation. Diagnostic study, Level III

Catalytic Oxidation of Volatile Organic Compounds over Porous Manganese Oxides Prepared via Sol-Gel Method

In this work, a set of binary and ternary manganese-copper-iron oxides was prepared via the citrate sol-gel synthesis. This facile technique allowed the preparation of mesoporous materials with promising performances for VOC oxidation in relatively short times and at mild temperatures. The physico-chemical properties of the samples were investigated by means of X-ray diffraction analysis, N2 physisorption at −196 °C, feld emission scanning electron microscopy, X-ray photoelectron spectroscopy, and H2 temperature-programmed reduction. The catalytic activity of the prepared samples was evaluated in the oxidation reaction of two VOC probe molecules (i.e., ethylene and propylene). Additionally, the reproducibility of the catalytic performance over the samples was studied through the realization of consecutive VOC catalytic oxidation runs