Extracellular Matrix News Volume 10.19 | May 23 2019

TOP STORY

Parenchymal and Stromal Tissue Regeneration of Tooth Organ by Pivotal Signals Reinstated in Decellularized Matrix

In contrast to the modest parenchyma formed by native adult progenitors, Alx3-restored cells in decellularized scaffolds not only produced vascularized stroma that involved vascular endothelial growth factor signaling, but also parenchymal dentin via the Wnt/β-catenin pathway. [Nat Mater] Abstract

(Ranked by impact factor of the journal)

A Mechano-Signaling Network Linking Microtubules, Myosin IIA Filaments and Integrin-Based Adhesions

Researchers showed that the effects of microtubules on two major types of cell-matrix adhesion, focal adhesions and podosomes, were mediated by KANK family proteins connecting the adhesion protein talin with microtubule tips. [Nat Mater] Abstract

Integrin Mechano-Chemical Signaling Generates Plasma Membrane Nanodomains That Promote Cell Spreading

Talin-mediated activation of the mechano-transducer vinculin was required for the coupling of the acto-myosin machinery to inner-leaflet lipids, thereby generating glycosylphosphatidylinositol-anchored protein (GPI-AP) nanoclusters. The authors showed that these nanoclusters were functional; disruption of their formation either in GPI-anchor remodeling mutants or in vinculin mutants impaired cell spreading and migration, hallmarks of integrin function. [Cell] Full Article | Graphical Abstract

Isolation and Propagation of Primary Human Cholangiocyte Organoids for the Generation of Bioengineered Biliary Tissue

The authors’ platform allowed the derivation of cholangiocyte organoids (COs) expressing key biliary markers and retaining functions of primary extra- or intrahepatic duct cholangiocytes within two weeks of isolation. COs were subsequently seeded on polyglycolic acid scaffolds or densified collagen constructs for four weeks to generate bioengineered tissue retaining biliary characteristics. [Nat Protoc] Abstract

A Change in ECM Composition Affects Sensory Organ Mechanics and Function

Investigators showed that the loss of pericardin, a major constituent of the chordotonal organ (ChO) ECM, alters the mechanical properties of the ChO resulting in short-wavelength buckling of the accessory cells upon muscle contraction and low compressive strain within the organ. [Cell Rep] Full Article | Graphical Abstract

mTORC1 Amplifies the ATF4-Dependent De Novo Serine-Glycine Pathway to Supply Glycine during TGF-β1-Induced Collagen Biosynthesis

Researchers showed that transforming growth factor-β1 (TGF-β1), the key pro-fibrotic cytokine implicated in multiple fibrotic conditions, increased the production of activating transcription factor 4 (ATF4), the transcriptional master regulator of amino acid metabolism, to supply glucose-derived glycine to meet the amino acid requirements associated with enhanced collagen production in response to myofibroblast differentiation. [Sci Signal] Full Article

Expression of Integrins to Control Migration Direction of Electrotaxis

Scientists established cell lines that stably express specific integrins and determined their responses to applied electric fields with a high throughput screen. Expression of specific integrins drove cells to migrate to the cathode or to the anode or to lose migration direction. [FASEB J] Abstract

Collagenolytic Matrix Metalloproteinases Antagonise Proteinase-Activated Receptor-2 Activation, Providing Insights into Extracellular Matrix Turnover

In proteinase-activated receptor (PAR)2-overexpressing SW1353 chondrocytes, researchers demonstrated that the activator peptide SLIGKV-NH2 induced rapid calcium flux, inflammatory gene expression, and the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 kinase. The corresponding matrix metalloproteinase cleavage-derived peptide exhibited no canonical activation, however they observed phosphorylation of ERK, providing evidence of biased agonism. [J Biol Chem] Abstract | Full Article

Runx1 Contributes to Articular Cartilage Maintenance by Enhancement of Cartilage Matrix Production and Suppression of Hypertrophic Differentiation

Runx1 enhanced cartilage matrix production in cooperation with Sox5, Sox6, and Sox9, and co-immunoprecipitation assays showed protein-protein binding between Runx1 and each Sox protein. Knockdown of Runx1 increased expression of a hypertrophic marker, Co10a1, in mouse articular cartilage and primary chondrocytes. [Sci Rep] Full Article

The Small GTPase Rac1 Increases Cell Surface Stiffness and Enhances 3D Migration into Extracellular Matrices

Investigators explored whether fibroblasts that were genetically deficient for Rac1 harbored altered mechanical properties, such as cellular deformability, intercellular adhesion forces and force exertion, and exhibit alterations in 3D motility. Rac1 knockout and control cells were analyzed for changes in deformability by applying an external force using an optical stretcher. [Sci Rep] Full Article

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Recent Advances in Cell Sheet Technology for Bone and Cartilage Regeneration: From Preparation to Application

Recent advances in utilizing cell sheet technology to regenerate bone or cartilage defects and bone-cartilage complex defects are reviewed. The key challenges and future research directions for the application of cell sheet technology in bone and cartilage regeneration are also discussed. [Int J Oral Sci] Abstract

Visit our reviews page to see a complete list of reviews in the extracellular matrix research field.

miRagen Presents Preclinical Data in Pulmonary Fibrosis Using Second Generation MicroRNA-29 Replacement Product Candidate

miRagen Therapeutics, Inc. announced that it will report new data demonstrating that systemic administration of its second-generation microRNA-29 mimic, the company’s pre-clinical micro-RNA targeted therapeutic candidate for idiopathic pulmonary fibrosis, efficiently reduced ECM deposition in a series of preclinical studies. [Press release from miRagen Therapeutics, Inc. discussing research presented at the 2019 American Thoracic Society (ATS) Conference, Dallas] Press Release

Santhera Starts Collaboration in Gene Therapy Research for Congenital Muscular Dystrophy with the Biozentrum, University of Basel, Co-Financed by Innosuisse

Santhera Pharmaceuticals announced its collaboration with the Biozentrum of the University of Basel to advance gene therapy research for the treatment of LAMA2-deficient congenital muscular dystrophy. The program is supported by public funding for innovation in Switzerland through a grant from Innosuisse – the Suisse Innovation Agency. [Santhera Pharmaceuticals] Press Release

CollPlant Launches New HQ and R&D Center in Israel

CollPlant is developing, manufacturing and commercializing products for tissue repair and organ manufacturing from its proprietary recombinant human collagen. The new R&D facilities will serve CollPlant for development of its product pipeline, including BioInks for 3D bioprinting of tissues and organs, and dermal fillers for medical aesthetics. [CollPlant Ltd.] Press Release

New US Patents Granted for RegenLab

Mr. Antoine Turzi, inventor, Regen Lab SA and RegenLab USA LLC announced that the United States Patent and Trademark Office has issued two new US patents covering its thrombin serum, platelet rich plasma (PRP) and hyaluronic acid (HA) technologies: Systems/methods for the preparation of PRP and HA in a single “all in one” device – the CELLULAR MATRIX™ technology* with tubes containing HA, a thixotropic gel and an anticoagulant: US Patent No. 10,272,139. [Regen Lab SA (PR Newswire Association LLC.)] Press Release

Brazilian Scientists Strive to Turn Politicians Into Allies

Brazil’s scientists are fighting back against President Jair Bolsonaro’s plans to slash funding for research and education programs. Researchers have joined with members of Brazil’s legislature, the National Congress, to highlight the strategic role that science, technology, and education play in the country’s economic and social development. [Nature News] Editorial

How European Scientists Will Spend €100 Billion

Politicians don’t win prizes for speed, but the European Union’s parliament and the leaders of its member states made record time this year when they hammered out an agreement that could supply researchers in Europe with more than €100 billion (US$113 billion) over seven years. [Nature News] Editorial

NSF, NASA, NIST Would Get Funding Boosts under House Spending Bill

The National Science Foundation (NSF) would get a 7% budget increase, and NASA a 3.8% bump, under a 2020 spending bill approved by an appropriations panel of the US House of Representatives. The bill rejects cuts to those and other federal research agencies proposed by President Donald Trump’s administration. [ScienceInsider] Editorial

NEW Bone and Muscle Interactions: The Mechanical and Beyond
August 16-18, 2019
Indianapolis, Indiana, United States

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NEW Postdoctoral Position – Experimental Systems Biology of Lung Regeneration & Fibrosis (Helmholtz Zentrum München)

Scientist – Matrix Biology (Stemcell Techonologies Inc.)

Postdoctoral Researchers – Hydrogel Chemistry & Kidney Tissue Engineering (Murdoch Children’s Research Institute)

Head of School – Biomedical Engineering (University of Sydney)

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

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

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

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

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

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

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