Endothelial Cell News Volume 5.04 | Feb 3 2020

TOP STORY

Cytotoxic CD4⁺ T Lymphocytes May Induce Endothelial Cell Apoptosis in Systemic Sclerosis

Investigators observed an accumulation of apoptotic cells in systemic sclerosis (SSc) tissues, suggesting that recurring cell death may contribute to tissue damage and remodeling in this fibrotic disease. HLA-DR expressing endothelial cells were frequent targets of apoptosis in SSc, consistent with the prominent vasculopathy seen in patients with this disease. [J Clin Invest] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Isolation of Tissue-Resident Vascular Endothelial Stem Cells from Mouse Liver

The authors describe an easy and reproducible protocol for isolation of different types of endothelial cells and CD157⁺ vascular-resident endothelial stem cells by mechano-enzymatic tissue digestion followed by fluorescence-activated cell sorting. [Nat Protoc] Abstract

Chronic Activation of Endothelial MAPK Disrupts Hematopoiesis via NFKB Dependent Inflammatory Stress Reversible by SCGF

Researchers identified endothelial cells as a crucial component in driving bone marrow inflammation and hematopoietic stem cell (HSC) dysfunction observed following myelosuppression. They demonstrated that sustained activation of endothelial MAPK caused NF-κB-dependent inflammatory stress response within the bone marrow, leading to significant HSC dysfunction including loss of engraftment ability and a myeloid-biased output. [Nat Commun] Full Article

Microchannel Network Hydrogel Induced Ischemic Blood Perfusion Connection

Hydrogel implantation in mouse and porcine models of hindlimb ischemia rescues severely damaged tissues by the ingrowth of neighboring host vessels with microchannel perfusion. This effect was guided by microchannel size-specific regenerative macrophage polarization with the consequent functional recovery of endothelial cells. [Nat Commun] Full Article

PRDM16 Orchestrates Angiogenesis via Neural Differentiation in the Developing Brain

Investigators demonstrated that neural differentiation and communication were required for vascular development. Regarding the cellular and molecular mechanism, results showed that PRDM16 activity determined the production of mature neurons and their specific positions in the neocortex. In the cortical plate, aberrant neurons failed to secrete modular calcium-binding protein 1. [Cell Death Differ] Abstract

Regulatory T Cells Condition Lymphatic Endothelia for Enhanced Transendothelial Migration

Researchers demonstrated a role for regulatory t cells (Tregs) through this pathway to condition the permissiveness of lymphatic endothelia for transendothelial migration, thus gating leukocyte traffic. Human Tregs share the same property with murine Tregs. [Cell Rep] Full Article | Graphical Abstract

Genetic Lineage Tracing Reveals Poor Angiogenic Potential of Cardiac Endothelial Cells

The authors observed that overexpression of the VEGF in the skeletal muscle potently stimulated angiogenesis, resulting in the formation of a massive number of new capillaries and arterioles. In contrast, response to the same dose of the same factor in the heart was blunted and consisted in a modest increase in the number of new arterioles. [Cardiovasc Res] Abstract | Graphical Abstract

Two Faces of Bivalent Domain Regulate VEGFA Responsiveness and Angiogenesis

By profiling the epigenetic landscape of endothelial cells during VEGF stimulation, the authors discovered that bivalent domains (BDs) were widespread in endothelial cells and preferentially marked genes responsive to VEGFA. The BDs responsive to VEGFA had more permissive chromatin environment comparing to other BDs. [Cell Death Dis] Full Article

Schnurri-3 Regulates BMP9-Induced Osteogenic Differentiation and Angiogenesis of Human Amniotic Mesenchymal Stem Cells through Runx2 and VEGF

Scientists conducted identified the effect of Schnurri-3 (Shn3) on bone morphogenetic protein 9 (BMP9)-induced osteogenic differentiation and angiogenesis in human amniotic mesenchymal stem cells (hAMSCs) and analyzed the responsible signaling pathway. The results from in vitro and in vivo experimentation showed that Shn3 inhibited BMP9-induced early and late osteogenic differentiation of hAMSCs, expression of osteogenesis-related factors, and subcutaneous ectopic bone formation from hAMSCs in nude mice. [Cell Death Dis] Full Article

Exosome-miR-155 Derived from Gastric Carcinoma Promotes Angiogenesis by Targeting C-MYB/VEGF Axis of Endothelial Cells

Investigators detected the expression of miR-155 and c-MYB was negatively correlated in gastric cancer (GC) and c-MYB was a direct target of miR-155. They next characterized the promotion effect of exosome-delivered miR-155 on angiogenesis and tumor growth in GC. [Mol Ther Nucleic Acids] Abstract | Full Article

Optimisation of Storage and Transportation Conditions of Cultured Corneal Endothelial Cells for Cell Replacement Therapy

Researchers investigated whether tissue engineered corneal endothelial cells could be preserved in hypothermic conditions. Human corneal endothelial cells were exposed to various temperatures in both adherent and suspension storage models. Optimal storage media and storage duration was tested along with post-storage viability. [Sci Rep] Full Article

Jedi-1 Deficiency Increases Sensory Neuron Excitability Through a Non-Cell Autonomous Mechanism

Investigators did not detect any morphological or functional changes in the glial cells or vasculature of Jedi-1 knockout mice. They observed changes in dorsal root ganglia neuron activity. In neurons from Jedi-1 knockout mice, there was an increase in the fraction of capsaicin-sensitive cells relative to wild type controls. [Sci Rep] Full Article

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The Life Cycle of Cancer-Associated Fibroblasts within the Tumor Stroma and Its Importance in Disease Outcome

The emergence, properties and clinical implications of cancer-associated fibroblasts activation are discussed, as well as research strategies used to characterize cancer-associated fibroblasts (CAFs) and current clinical efforts to alter CAF function as a therapeutic strategy. [Br J Cancer] Abstract

Heme Oxygenase Dependent Bilirubin Generation in Vascular Cells: A Role in Preventing Endothelial Dysfunction in Local Tissue Microenvironment?

Understanding the molecular actions of bilirubin may critically improve the management not only of key cardiovascular diseases, but also provide insights into a broad spectrum of pathologies driven by endothelial dysfunction. In this context, therapeutic interventions aimed at mildly increasing serum bilirubin as well as bilirubin generated endogenously by endothelial HMOX1 should be considered. [Front Physiol] Full Article

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Bio-Thera Solutions Announces Positive Top-Line Results for BAT1706, a Proposed Biosimilar to Avastin^®

Bio-Thera Solutions announced that the Phase III clinical trial comparing the safety and efficacy of BAT1706 versus Avastin^® met its primary endpoint. BAT1706 is being developed by Bio-Thera Solutions as a proposed biosimilar to Avastin^®. The trial demonstrated equivalence in overall response rate for the first-line treatment of patients with non-squamous non-small cell lung cancer. [Bio-Thera Solutions {BusinssWire, Inc.)] Press Release

Acceleron Announces Sotatercept Achieved Primary and Secondary Endpoints in the PULSAR Phase II Placebo-Controlled Trial in Patients with Pulmonary Arterial Hypertension

Acceleron Pharma, Inc. announced that the PULSAR Phase II trial of sotatercept met its primary and key secondary endpoints in patients with pulmonary arterial hypertension. In patients on stable background PAH-specific therapies, sotatercept demonstrated a statistically significant reduction in pulmonary vascular resistance, the trial’s primary endpoint, at week 24 versus placebo. [Acceleron Pharma, Inc.] Press Release

Akari Therapeutics Announces Preclinical Ophthalmic Data Showing Nomacopan Reduces Both Vascular Endothelial Growth Factor (VEGF) and Retinal Inflammation Supporting Nomacopan as a Potential Treatment Option for Back-of-the-Eye Diseases

Akari Therapeutics, Plc announced new pre-clinical data indicating that nomacopan significantly reduced both retinal inflammation and intraocular VEGF. [Akari Therapeutics, Plc] Press Release

Genentech Submits Supplemental Biologics License Application to the FDA for Tecentriq in Combination with Avastin for the Most Common Form of Liver Cancer

Genentech, a member of the Roche Group, announced the completion of a supplemental Biologics License Application submission to the FDA for Tecentriq^® in combination with Avastin^® for the treatment of people with unresectable hepatocellular carcinoma who have not received prior systemic therapy. [Genentech] Press Release

US Prosecutor Leading China Probe Explains Effort That Led to Charges against Harvard Chemist

The US government isn’t prosecuting Charles Lieber because he’s a world-renowned inorganic chemist at Harvard University, says the US attorney who last week drew headlines by charging Lieber with making false statements about his ties to Chinese research institutions. Nor does the Department of Justice think for one minute that Lieber is a spy. [ScienceInsider] Editorial

Cash From Cannabis Companies Creates Conflicted Researchers

Imagine that scientists charged with doing research on tobacco’s health implications were funded by tobacco companies. In fact, the tobacco industry used this tactic for decades to cast doubt on the adverse health effects of smoking. But today it would be an outrageous conflict of interest – research on addictive drugs shouldn’t be paid for by people who stand to profit from selling them. Yet this is exactly what is happening with cannabis. [STAT News] Editorial

Chan Zuckerberg Initiative to Fund 30 Patient Groups, Aiming to Build a Model for Tackling Rare Diseases

On January 3^rd, Mark Zuckerberg and his spouse Dr. Priscilla Chan’s philanthropic vehicle announced a set of grants that executives there hope will create a model for tackling any rare disease: financing patient-led groups, and giving them training and resources. [STAT News] Editorial

NEW First International STEMNET Meeting
May 6-8, 2020
Padua, Italy

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NEW Postdoctoral Researcher – Human Atherosclerosis (Karolinska Institutet)

PhD Position – Aging (Lausanne University Hospital)

Postdoctoral Fellow – Vascular Dysfunction in Neurodegeneration (Lund University)

Postdoctoral Researcher (University of Illinois at Chicago)

Tenure Track Faculty – Endothelial Cell Regeneration (Ohio State University)

Post-Doctoral Fellow – Metabolic Regulation of Vascular Formation (Oklahoma Medical Research Foundation)

Postdoctoral Position (University Hospital of Muenster)

Postdoctoral Research Fellow – Pulmonary Vascular Diseases (Boston Children’s Hospital)

PhD Student – Aortic Disease (University Hospital of Cologne)

Postdoctoral Research Fellow – Aortic Disease (University Hospital of Cologne)

Postdoctoral Positions – Bioinformatics and Vascular Biology (KU Leuven)

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