Volume 6.21 | Jun 4

Extracellular Matrix News 6.21 June 4, 2015
Extracellular Matrix News
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Study Demonstrates Drug-Induced Tissue Regeneration
Scientists focused on the HIF-1a protein, the expression of which is markedly increased before and after injury in the MRL mouse. Under normal oxygen conditions, HIF-1a is degraded by prolyl hydroxylases (PHDs). Stabilization of HIF-1a levels can be accomplished through inhibition of PHDs. [Press release from Main Line Health discussing online prepublication in Science Translational Medicine] Press Release | Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
LPP Inhibits Collective Cell Migration during Lung Cancer Dissemination
Researchers showed that lipoma preferred partner (LPP) degraded N-cadherin in lung cancer, PC14PE6 cells via regulating the expression of matrix metalloproteinase 15, and loss-of-LPP increases collective cell migration and dissemination consequently. [Oncogene] Abstract

Engineered Composite Tissue as a Bioartificial Limb Graft
To create an autologous, bio-artificial graft based on native extracellular matrix and patient derived cells, scientists decellularized rat and primate forearms by detergent perfusion and yielded acellular scaffolds with preserved composite architecture. They then repopulated muscle and vasculature with cells of appropriate phenotypes, and matured the composite tissue in a perfusion bioreactor under electrical stimulation in vitro. [Biomaterials] Abstract | Press Release | Video

The Microwell-Mesh: A Novel Device and Protocol for the High Throughput Manufacturing of Cartilage Microtissues
The authors describe the first microwell platform that incorporates a mesh to retain microtissues within discrete microwells; the microwell-mesh. They showed that bonding a nylon mesh with an appropriate pore size over the microwell openings allows single cells to pass through the mesh into the microwells during the seeding process, but subsequently retains assembled microtissues within discrete microwells. [Biomaterials] Full Article

ADAMTS9-Mediated Extracellular Matrix Dynamics Regulates Umbilical Cord Vascular Smooth Muscle Differentiation and Rotation
The secreted metalloprotease ADAMTS9 was shown to be necessary for murine umbilical cord vascular development. Restricting it to the cell surface using a gene trap allele, Adamts9Gt, impaired umbilical vessel elongation and radial growth via reduced versican proteolysis and accumulation of extracellular matrix. [Cell Rep] Full Article | Graphical Abstract

Modulation of Extracellular Matrix in Cancer Is Associated with Enhanced Tumor Cell Targeting by Bacteriophage Vectors
Researchers investigated and quantified the effect of extracellular matrix (ECM) depletion on ECM composition (including collagen type I, hyaluronic acid, fibronectin and laminin), and how adeno-associated virus/phage adsorption, internalization, gene expression and therapeutic efficacy are subsequently affected. [Mol Cancer] Full Article

Decoupling the Role of Stiffness from Other Hydroxyapatite Signaling Cues in Periosteal Derived Stem Cell Differentiation
To isolate the contribution of mechanical cues from other hydroxyapatite (HA)-derived signals, scientists developed and characterized composite HA/gelatin scaffolds with different mineral contents along with a set of stiffness-matched HA-free gelatin scaffolds. Samples were seeded with human periosteal derived progenitor cells and cultured over seven days, analyzing their resultant morphology and gene expression. [Sci Rep] Full Article

Extracellular Matrix Can Recover the Downregulation of Adhesion Molecules after Cell Detachment and Enhance Endothelial Cell Engraftment
Researchers investigated if processes involved in cell preparation could initiate downregulation of adhesion-related survival signals, and further affect cell engraftment after transplantation. They demonstrated that cell detachment can cause downregulation of cell adhesion and extracellular matrix molecules, but no obvious cell anoikis, a form of apoptosis after cell detachment, was observed. [Sci Rep] Full Article

Fibrin Supports Human Fetal Islet-Epithelial Cell Differentiation via p70s6k and Promotes Vascular Formation during Transplantation
Scientists investigated how fibrin promotes human fetal pancreatic cell differentiation in vitro and in vivo. Fibrin-cultured human fetal pancreatic cells had significantly increased expression of PDX-1, glucagon, insulin, and VEGF-A, along with increased integrin αVβ3 and phosphorylated FAK and p70s6k. [Lab Invest] Abstract

TGFβ1 Exacerbates Blood–Brain Barrier Permeability in a Mouse Model of Hepatic Encephalopathy via Upregulation of MMP9 and Downregulation of Claudin-5
Researchers assessed whether increased circulating transforming growth factor β1 (TGFβ1) drives changes in tight junction protein expression and matrix metalloproteinase 9 (MMP9) activity following acute liver failure. [Lab Invest] Abstract

Second Harmonic Generation Microscopy Reveals Altered Collagen Microstructure in Usual Interstitial Pneumonia versus Healthy Lung
Two-photon second harmonic generation (SHG) and excitation fluorescence microscopies were used to interrogate and quantify differences between intrinsic fibrillar collagen and elastin matrix signals in healthy, cryptogenic organizing pneumonia, and usual interstitial pneumonia lung. [Resp Res] Abstract | Full Article

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Consequences of Metabolic and Oxidative Modifications of Cartilage Tissue
A general picture starts to emerge indicating that biochemical changes in proteins constitute an early event that compromises the anatomical organization and viscoelasticity of cartilage, thereby affecting its ability to sustain pressure and, ultimately, impeding its overall bio-performance. [Nat Rev Rheumatol] Abstract

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Azrieli Foundation Donates $10 Million for Hebrew University Research
The Azrieli Foundation has donated $10 million to fund innovative research at the Hebrew University of Jerusalem’s newly inaugurated Azrieli Center for Stem Cells and Genetic Research. [Hebrew University of Jerusalem] Press Release

Asana Medical, Inc. Secures Core Technology License for Treatment of IBD Including Ulcerative Colitis
Asana Medical, Inc. has obtained a world-wide, field specific, exclusive license from the University of Pittsburgh on multiple patents and patent applications covering methods and for treating inflammatory bowel disease (IBD) without a colectomy, including the use of extracellular matrix-derived gels and their methods for preparation and sterilization. [Asana Medical, Inc.] Press Release

OrthoTrophix Completed Subject Enrollment of the Phase II Clinical Trial of a New Cartilage Repair Therapeutic for Knee Osteoarthritis
OrthoTrophix, Inc. announced that the company completed subject enrollment and all scheduled dosing in its Phase II clinical study of TPX-100 in subjects with bilateral osteoarthritis of the knee. [OrthoTrophix, Inc.] Press Release

Ocata Therapeutics Receives Three New U.S. Patents for its RPE Therapy for Macular Degenerative Diseases
Ocata Therapeutics, Inc. announced that the United States (U.S.) Patent and Trademark Office issued three new U.S. Patents, Nos. 9,040,770, 9,040,039 and 9,040,038, which expand the scope of protection of the four previously issued U.S. patents covering its retinal pigment epithelium (RPE) transplant technology. [Ocata Therapeutics, Inc.] Press Release

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NEW 2nd Matrix Biology Ireland (MBI) 2015
December 1-4, 2015
Dublin, Ireland

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NEW Postdoctoral Position – Proteoglycan and Dislocations (Inserm)

NEW Assistant Professor – Instructive Biomaterials Engineering (Maastricht University)

PhD Studentship – Polymeric Biomaterials and their Biological Evaluation (Helmholtz-Zentrum Geesthacht)

PhD Positions – Cartilage Regeneration in Joints and Intervertebral Disc Diseases (Percuros B.V.)

Assistant Professor – Instructive Biomaterials Engineering (Maastricht University)

Faculty Positions – Regenerative Medicine for Kidney or Liver Regeneration or Transplantation (University of Texas Health Science Center at Houston)

PhD Position – Tumor Biology (University of Duisburg-Essen)

Postdoctoral Fellow – Disseminated Tumor Cell Biology (Fred Hutchinson Cancer Research Center)

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