Extracellular Matrix News Volume 10.16 | May 2 2019

TOP STORY

Nanofiber-Hydrogel Composite-Mediated Angiogenesis for Soft Tissue Reconstruction

By incorporating interfacial bonding between electrospun poly(ε-caprolactone) fibers and a hyaluronic acid hydrogel network, scientists generated a composite that mimics the microarchitecture and mechanical properties of soft tissue ECM. [Sci Transl Med] Abstract

(Ranked by impact factor of the journal)

Intercellular Instructed-Assembly Mimics Protein Dynamics to Induce Cell Spheroids

Researchers showed that intercellular morphological transition of peptide assemblies mimic the unfolding of fibronectin, thus enabling formation of spheroids from a monolayer of cells. Further mechanism study indicated that the intercellular assemblies interacted with multiple ECM components to drive the formation of the cell spheroids. [J Am Chem Soc] Abstract | Graphical Abstract

Abrogation of Myofibroblast Activities in Metastasis and Fibrosis by Methyltransferase Inhibition

Investigators found that inhibitors of methyltransferases prevented myofibroblast activity in the ECM, both in cell culture and in vivo. In a mouse breast cancer model, the inhibitor sinefungin reduced both the myofibroblast activity in the tumor stroma, and the metastatic burden in the lung. [Int J Cancer] Abstract

CD13 Tethers the IQGAP1-ARF6-EFA6 Complex to the Plasma Membrane to Promote ARF6 Activation, β1 Integrin Recycling, and Cell Migration

The authors found that the cell surface antigen CD13, a multifunctional transmembrane molecule that regulates cell-cell adhesion and receptor-mediated endocytosis, also promoted cell migration and colocalized with β1 integrin at sites of cell adhesion and at the leading edge. [Sci Signal] Abstract

The Laminin Interactome: A Multifactorial Laminin-Binding Strategy by Nontypeable Haemophilus influenzae for Effective Adherence and Colonization

Laminin-binding proteins (Lbps), elongation factor thermo-unstable, L-lactate dehydrogenase, protein D and peptidoglycan-associated lipoprotein P6 exhibited interactions with laminin, and mediated nontypeable Haemophilus influenzae laminin-dependent adherence to pulmonary epithelial cell lines. [J Infect Dis] Abstract

Beta1 Integrin Blockade Overcomes Doxorubicin Resistance in Human T-Cell Acute Lymphoblastic Leukemia

Scientists demonstrated that interactions of human T-cell acute lymphoblastic leukemia cell lines and primary blasts with three-dimensional matrices including Matrigel and collagen type I gel promote their resistance to doxorubicin via β1 integrin. [Cell Death Dis] Full Article

Amnion Membrane Organ-on-Chip: An Innovative Approach to Study Cellular Interactions

The authors developed an amnion membrane organ-on-chip (AM-OOC) and tested the interactive and transition properties of primary human amnion epithelial cells and amnion mesenchymal cells under normal and oxidative stress conditions. AM-OOC contained two chambers connected by type IV collagen-coated microchannels, allowing independent culture conditions that permitted cellular migration and interactions. [FASEB J] Abstract

Deacetylation of S6 Kinase Promotes High Glucose-Induced Glomerular Mesangial Cell Hypertrophy and Matrix Protein Accumulation

To determine the mechanism of S6 kinase deacetylation, researchers found that TSA, a pan HDAC inhibitor, blocked all high glucose-induced effects. High glucose increased the expression and association of HDAC1 with S6 kinase. HDAC1 decreased the acetylation of S6 kinase and mimicked the effects of high glucose, resulting in mesangial cell hypertrophy and expression of fibronectin and collagen I. [J Biol Chem] Abstract | Full Article

Reduced Basal Nitric Oxide Production Induces Precancerous Mammary Lesions via ERBB2 and TGFβ

Investigators showed that the basal level of nitric oxide (NO) in breast cells plummetted during cancer progression due to reduction of the NO synthase cofactor, BH4, under oxidative stress. Importantly, pharmacological deprivation of NO in prepubertal to pubertal animals stiffened the ECM and induced precancerous lesions in the mammary tissues. [Sci Rep] Full Article

Estrogen-Related Receptor Alpha Induces Epithelial-Mesenchymal Transition through Cancer-Stromal Interactions in Endometrial Cancer

Estrogen-related receptor alpha (ERRα)/proliferator-activated receptor gamma coactivator 1-alpha overexpression increased the expression of epithelial-mesenchymal transition (EMT)-associated factors after transforming growth factor-beta (TGF-β) exposure; however, it decreased E-cadherin at the protein level. ERRα knockdown suppressed EMT-associated factors in the presence of TGF-β, whereas E-cadherin remained unchanged. [Sci Rep] Full Article

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3D Bioprinting: From Benches to Translational Applications

The authors cover the history of bioprinting and the most recent advances in instrumentation and methods. They then focus on the requirements for bioinks and cells to achieve optimal fabrication of biomimetic constructs. [Small] Abstract

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miRagen Therapeutics Announces New Data Supporting the Potential Use of Remlarsen to Prevent Corneal Fibrosis

miRagen Therapeutics, Inc. announced data from a preclinical study of remlarsen, a microRNA-29 replacement, exploring the anti-fibrotic effects of remlarsen in the cornea of rats after corneal ulceration. miR-29b is an antifibrotic microRNA that inhibits EMT, FMT and collagen expression in multiple organs and tissues. [Press release from miRagen Therapeutics, Inc. discussing research presented at the 2019 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, Vancouver] Press Release

Latest Wound Care Research from Organogenesis Highlighted

Organogenesis Holdings Inc. announced that the latest research on NuShield^® and PuraPly^® Antimicrobial will be presented. [Press release from Organogenesis Holdings Inc. discussing research to be presented at the Symposium on Advanced Wound Care Spring | Wound Healing Society (SAWC Spring | WHS) 2019 Meeting, San Antonio] Press Release

Krystal Biotech Announces Five Presentations of Clinical and Preclinical Data

Krystal Biotech Inc. announced presentations of clinical data for KB103 to treat dystrophic epidermolysis bullosa, and preclinical data on KB105 for the treatment of autosomal recessive congenital ichthyosis and KB104 for the treatment of Netherton syndrome. [Press release from Krystal Biotech Inc. discussing research to be presented at the Society for Investigative Dermatology 77^th Annual Meeting, Chicago] Press Release

Rocket Pharmaceuticals Receives Funding from the California Institute for Regenerative Medicine (CIRM)

Rocket Pharmaceuticals, Inc. announced that CIRM has awarded Rocket a $6.5mm CLIN2 grant award to support the clinical development of gene therapy for leukocyte adhesion deficiency-I (LAD-I). Severe LAD-I is a rare, autosomal recessive pediatric disease caused by a mutation of the ITGB2 gene that encodes for the Beta-2 Integrin component CD18. [Rocket Pharmaceuticals, Inc.] Press Release

Avedro Completes Enrollment in Pivotal US Phase III Epi-On Corneal Cross-Linking Clinical Trial for Progressive Keratoconus

Avedro, Inc. announced that the company has completed patient enrollment in a pivotal Phase III clinical trial to evaluate the safety and efficacy of an epithelium-on (Epi-On) corneal cross-linking procedure for the treatment of progressive keratoconus. [Avedro, Inc.] Press Release

Phoenix Tissue Repair Receives FDA Fast Track Designation for PTR-01 for the Treatment of Dystrophic Epidermolysis Bullosa (DEB) and Provides Updates on the Phase I/II Clinical Study

Phoenix Tissue Repair, Inc. announced that the FDA has granted fast track designation for PTR-01, an investigational protein replacement therapy designed to treat recessive DEB. DEB is a rare genetic disorder symptomatic from birth that is caused by mutations in the gene for a protein called collagen type VII. [Phoenix Tissue Repair, Inc. (PR Newswire Association LLC.)] Press Release

Organogenesis Receives Innovative Technology Contract from Vizient

Organogenesis Holdings Inc. announced that it has received an Innovative Technology contract from Vizient, Inc. for its portfolio of advanced wound care and surgical and sports medicine products. [Organogenesis Holdings Inc.] Press Release

Shake-Up at NIH: Term Limits for Important Positions Would Open New Opportunities for Women, Minorities

The NIH is aiming to shake up its intramural program, the largest collection of biomedical researchers in the world, by imposing term limits on midlevel leadership positions. Starting next year, the 272 lab and branch chiefs who oversee NIH’s intramural research will be limited to 12-year terms. [ScienceInsider] Editorial

Senator’s Queries Prompt NIH and NSF to Clarify How They Monitor Foreign Research Ties

Responding to the rising concern within Congress that foreign governments are taking advantage of the open US research enterprise, the National Institutes of Health (NIH) and the National Science Foundation (NSF) have recently tweaked their grantmaking process to better monitor the foreign ties of the researchers they fund. [ScienceInsider] Editorial

NEW Understanding the Molecular Mechanisms that Underpin Wound Repair and Regeneration
June 9-14, 2019
New London, New Hampshire, United States

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NEW Postdoctoral Fellowship – Renal Extracellular Matrix Research (Vanderbilt University Medical Center)

NEW Postdoctoral Associate – Pathogenesis of Kidney Injurty & Fibrosis (University of Connecticut Health Center)

Associate Professor/Professor – Cell & Molecular Biology (University of Illinois at Chicago)

Lecturer – Stem Cell Biology/Regenerative Medicine (The University of Manchester)

Postdoctoral Fellow – Ligand and Integrin Therapeutics (Boston Children’s Hospital)

Postdoctoral Fellow – Gene Function in Fibrosis & Wound Healing (Oklahoma Medical Research Foundation)

Tenure-Track Lecturer – Molecular Biology (University of Cyprus)

Postdoctoral Position – Vascular Tissue Engineering (BioTis)

Faculty Position – Department of Bioengineering (University of Pittsburgh)

Postdoctoral Scholar – Computational Modeling of Cell-Matrix Interactions (Washington University, St. Louis)

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