Extracellular Matrix News Volume 8.23 | Jun 15 2017

TOP STORY

Artificial Cartilage under Tension as Strong as Natural

Researchers created a lab-grown tissue similar to natural cartilage by giving it a bit of a stretch. The tissue, grown under tension but without a supporting scaffold, showed similar mechanical and biochemical properties to natural cartilage. [Press release from the University of California, Davis discussing online prepublication in Nature Materials] Press Release | Abstract

(Ranked by impact factor of the journal)

ISDoT: In Situ Decellularization of Tissues for High-Resolution Imaging and Proteomic Analysis of Native Extracellular Matrix

Scientists present a fast and efficient approach to enhance the study of ECM composition and structure. Termed in situ decellularization of tissues (ISDoT), it allowed whole organs to be decellularized, leaving native ECM architecture intact. [Nat Med] Abstract | Press Release

Isoprenylcysteine Carboxylmethyltransferase Function Is Essential for RAB4A-Mediated Integrin β3 Recycling, Cell Migration and Cancer Metastasis

Researchers found that inhibition of isoprenylcysteine carboxylmethyltransferase (ICMT) significantly reduced cell migration in vitro and cancer invasion and metastasis in vivo. This role of ICMT was found to be mediated by RAB4A, an essential regulator of the fast recycling of integrin β3. Integrin β3 regulated cell polarity and migration when localized appropriately to the plasma membrane, thereby having an essential role in cancer metastasis. [Oncogene] Full Article

Oncogenic K-Ras Upregulates ITGA6 Expression via FOSL1 to Induce Anoikis Resistance and Synergizes with αV-Class Integrins to Promote EMT

Investigators showed that oncogenic K-Ras^V12 upregulates α6-integrin expression in Madin–Darby canine kidney (MDCK) cells via activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase/Fos-related antigen 1-signaling cascade. Activated α6-integrins promoted metastatic capacity and anoikis resistance, and led to perturbed growth of MDCK cysts. [Oncogene] Full Article

Extracellular Signal-Regulated Kinase 5 Associates with Casein Kinase II to Regulate GPIb-IX-Mediated Platelet Activation via the PTEN/PI3K/Akt Pathway

The functions of extracellular signal-regulated kinase 5 (ERK5) in glycoprotein (GP)Ib-IX-mediated human platelet activation were assessed using botrocetin/VWF, ristocetin/VWF, or platelet adhesion to VWF under shear stress in the presence of a specific inhibitor of ERK5. The phosphorylation levels of ERK5 were significantly enhanced in human platelets stimulated with botrocetin/VWF or ristocetin/VWF. [J Thromb Haemost] Abstract

Direct Evidence for Cell Adhesion-Mediated Radioresistance (CAM-RR) on the Level of Individual Integrin β1 Clusters

As integrins are the key mediators of cell adhesion and mechanosensing, they originate the molecular signaling towards chromatin remodeling in response to a cell’s microenvironment. The authors investigated this molecular origin that leads to “cell-adhesion-mediated-radio-resistance” (CAM-RR) by investigating the distribution of integrins at the single molecule level and show that cells cultured in 2D keep a lower fraction of integrin β1 in clusters and maintain a less defined cluster status than 3D cultured cells. [Sci Rep] Full Article

Tumstatin Regulates the Angiogenic and Inflammatory Potential of Airway Smooth Muscle Extracellular Matrix

Neutrophils and endothelial cells were seeded on decellularized ECM of non-asthmatic (NA) or asthmatic (Archive) airway smooth muscle (ASM) cells previously exposed to tumstatin in the presence or absence of a broad matrix metalloproteinase inhibitor, Marimastat. The presence of tumstatin during ECM deposition affected neutrophil and endothelial cell properties on both NA and A ASM-derived matrices and this was only partly due to MMP activity. [J Cell Mol Med] Full Article

Extracellular Matrix Protein Laminin Enhances Mesenchymal Stem Cell (MSC) Paracrine Function through αvβ3/CD61 Integrin to Reduce Cardiomyocyte Apoptosis

The authors found that placenta-derived multipotent cells (PDMCs) significantly reduced cardiomyocyte apoptosis and reactive oxygen species production through the paracrine factors GRO-α, HGF and IL-8. The enhancement of PDMC paracrine function by laminin was mediated through αvβ3 integrin, with involvement of the signaling pathways of JNK, for GRO-α and IL-8 secretion, and PI3K/AKT, for HGF secretion. [J Cell Mol Med] Full Article

Composite Scaffolds of Mineralized Natural Extracellular Matrix on True Bone Ceramic Induce Bone Regeneration via Smad1/5/8 and ERK1/2 Pathways

Scientists designed a novel tissue-derived ECM scaffold fabricated by depositing porcine small intestinal submucosa (SIS) ECM on true bone ceramic (TBC), which was followed by mineralization treatment (mSIS/TBC). In vitro, compared with pure TBC, mSIS/TBC promoted cell proliferation, cell viability, and osteoblastic differentiation of the newly-seeded rat bone marrow stem cells (BMSCs), and upregulation of the mRNA level of osteogenesis-related genes. [Tissue Eng Part A] Abstract

Exposure to Bordetella pertussis Adenylate Cyclase Toxin Affects Integrin-Mediated Adhesion and Mechanics in Alveolar Epithelial Cells

Investigators used a recently proposed multiple bond force spectroscopy with an atomic force microscope to assess the early phase of cell adhesion and cell rigidity in alveolar epithelial cells for toxin exposure less than one hour. At 30 minutes of exposure, CyaA toxin had a minimal effect on cell viability at the physiological CyaA concentration of 0.5nM, but a significant effect at 10nM. [Biol Cell] Abstract

Clinical Implications of Compounds Designed to Inhibit ECM-Modifying Metalloproteinases

The correlation of matrix metalloproteinase (MMP) and a disintegrin and metalloprotease (ADAM) activity to a variety of diseases has instigated numerous drug development programs. However, broad-based and Zn²⁺-chelating MMP and ADAM inhibitors have fared poorly in the clinic. Selective MMP and ADAM inhibitors have been described recently based on (a) antibodies or antibody fragments or (b) small molecules designed to take advantage of protease secondary binding sites (exosites) or allosteric sites. [Proteomics] Abstract

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

Fibrocell Receives Rare Pediatric Disease Designation from FDA for FCX-013 for Treatment of Localized Scleroderma

Fibrocell Science, Inc. announced that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation to FCX-013, Fibrocell’s gene therapy candidate for the treatment of moderate to severe localized scleroderma—a chronic autoimmune disease characterized by thickening of the skin and connective tissue. [Fibrocell Science, Inc.] Press Release

Excellagen^® Receives USPTO Notice of Allowance for a New Patent Application Covering Blood Platelet Activation & Endogeneous Growth Factor Release for Wound Repair and Tissue Regeneration

Taxus Cardium Pharmaceuticals Group Inc. and its operating unit Activation Therapeutics announced that a Notice of Allowance has been received from the U.S. Patent and Trademark Office (USPTO) for a new patent application entitled “Flowable Formulations for Tissue Repair and Regeneration.” [Taxus Cardium Pharmaceuticals Group Inc.] Press Release

Texas Has Sanctioned Unapproved Stem Cell Therapies. Will It Change Anything?

Texas Governor Greg Abbott signed a bill allowing clinics and companies in the state to offer people unproven stem cell interventions without the testing and approval required under federal law. Like the “right to try” laws that have sprung up in more than 30 states, the measure is meant to give desperately ill patients access to experimental treatments without oversight from the U.S. Food and Drug Administration. [ScienceInsider] Editorial

Empty Rhetoric over Data Sharing Slows Science

Government agencies lack the funds to build platforms for data sharing and resist taking responsibility for such infrastructure. They may hope that universities will host data, but the development of institutional repositories is patchy, and to rely on them is effectively to discourage common data standards and curation. [Nature News] Editorial

Can Fake Names Tease Out NIH Reviewer Bias?

When the label “white male” is attached to a research grant application, do peer reviewers give it a better score? That’s the question psychologist Patricia Devine of the University of Wisconsin in Madison has spent the past four years, and more than $1 million from the National Institutes of Health (NIH) in Bethesda, Maryland, trying to answer with an unusual experiment. [ScienceInsider] Editorial

Curiosity and Irritation Meet Macron’s Effort to Lure Foreign Scientists to France

The French government unveiled a website aimed at attracting foreign scientists with four-year grants worth up to €1.5 million each. [ScienceInsider] Editorial

NEW Gordon Research Conferences: Bioinspired Materials
June 24-29, 2018
Les Diablerets, Switzerland

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellowship – Tissue Fibrosis (University of California, San Francisco)

Group Leaders – Multiple Areas (French National Center for Scientific Research)

Assistant Professor – Biofilms (University of Maryland)

Postdoctoral Researcher – Degenerative Disc Disease (NUI Galway)

Part Time Faculty – Developmental Biology (Boston College Biology Department)

Postdoctoral Fellow – Proteoglycan Remodeling (University of Alberta)

Postdoctoral Research Fellow – Tendon and Connective Tissue Biology (Weill Cornell Medical College)

Postdoctoral Associate – Molecular and Cell Biology (Stony Brook University)

PhD Position – Extracellular Matrix in Cancer Progression (University of Copenhagen)

Biomaterials Scientist – Tissue Engineering (VitroLabs Inc.)

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