Extracellular Matrix News Volume 10.07 | Feb 28 2019

TOP STORY

Breast Cancer Cells Rely on Environmental Pyruvate to Shape the Metastatic Niche

Researchers showed that breast cancer cells relied on the nutrient pyruvate to drive collagen-based remodeling of the ECM in the lung metastatic niche. Specifically, they discovered that pyruvate uptake induced the production of α-ketoglutarate. This metabolite in turn activated collagen hydroxylation by increasing the activity of the enzyme collagen prolyl-4-hydroxylase. [Nature] Abstract

(Ranked by impact factor of the journal)

Secreted Metalloproteases ADAMTS9 and ADAMTS20 Have a Non-Canonical Role in Ciliary Vesicle Growth during Ciliogenesis

CRISPR-Cas9 inactivation of ADAMTS9 impaired ciliogenesis in RPE-1 cells, which was restored by catalytically active ADAMTS9 or ADAMTS20 acting in trans, but not by their proteolytically inactive mutants. Their mutagenesis in mice impaired neural and yolk sac ciliogenesis, leading to morphogenetic anomalies resulting from impaired hedgehog signaling, which is transduced by primary cilia. [Nat Commun] Full Article

An Atlas of the Aging Lung Mapped by Single Cell Transcriptomics and Deep Tissue Proteomics

Scientists observed cell type-specific effects of aging, uncovering increased cholesterol biosynthesis in type-2 pneumocytes and lipofibroblasts and altered relative frequency of airway epithelial cells as hallmarks of lung aging. Proteomic profiling revealed ECM remodeling in old mice, including increased collagen IV and XVI and decreased Fraser syndrome complex proteins and collagen XIV. [Nat Commun] Full Article | Press Release

p16^Ink4a Deletion in Cells of the Intervertebral Disc Affects Their Matrix Homeostasis and Senescence Associated Secretory Phenotype without Altering Onset of Senescence

Investigators studied the spinal-phenotype of 18-month-old mice with conditional deletion of p16^Ink4a in the disc driven by Acan-CreERT2 (cKO). The cKO mice exhibited changes in functional attributes of aggrecan as well as in collagen composition of the intervertebral disc. [Matrix Biol] Abstract

Process- and Bio-Inspired Hydrogels for 3D Bioprinting of Soft Free-Standing Neural and Glial Tissues

The novel filler-free bioinks were designed by combining natural polymers for ECM biomimicry with synthetic polymers to endow desirable rheological properties for 3D bioprinting. Crosslinking of thiolated Pluronic F-127 with dopamine-conjugated (DC) gelatin and DC hyaluronic acid through a thiol-catechol reaction resulted in thermally gelling bioinks with Herschel-Bulkley fluid rheological behavior. [Biofabrication] Abstract

EMT Is Associated with an Epigenetic Signature of ECM Remodeling Genes

The authors studied the overall modulations of gene expression and epigenetic modifications in four different epithelial-mesenchymal transition (EMT)-induced cell models issued from different tissues and using different inducers of EMT. [Cell Death Dis] Full Article

Integrin α11 in Pancreatic Stellate Cells Regulates Tumor Stroma Interaction in Pancreatic Cancer

Primary human PSCs (hPSCs) activated with either TGF-β or pancreatic cancer cell-conditioned medium (CM) resulted in the significant up-regulation of integrin subunit α 11 (ITGA11) and various cancer-associated fibroblast markers. Short hairpin RNA-mediated stable ITGA11 knockdown in hPSCs significantly inhibited TGF-β- and PANC-1 CM-mediated activation at both gene and protein levels of ECM, cytokines, and adhesion molecules. [FASEB J] Abstract

Downregulation of Lysyl Oxidase and Lysyl Oxidase-Like Protein 2 Suppressed the Migration and Invasion of Trophoblasts by Activating the TGF-β/Collagen Pathway in Preeclampsia

Mechanistically, collagen production was induced in lysyl oxidase (LOX) – or LOX-like protein 2-downregulated trophoblast cells through activation of the TGF-β1/Smad3 pathway. Additionally, induced collagen production and activated TGF-β1/Smad3 were observed in clinical samples from preeclamptic placentas. [Exp Mol Med] Full Article

Stem-Cell Therapy for Esophageal Anastomotic Leakage by Autografting Stromal Cells in Fibrin Scaffold

Due to the healing effects of mesenchymal stromal cells (MSCs) and supporting capability of fibrin scaffolds (FSs), scientists evaluated the efficacy of a stem-cell therapy for esophageal anastomotic leakage by engrafting adult and autologous MSCs in FS and investigated the potential mechanism. [Stem Cells Transl Med] Full Article

Pre-Clinical Evaluation of CBD-NT3 Modified Collagen Scaffolds in Completely Spinal Cord Transected Non-Human Primates

The acute thoracic complete transection model in rhesus monkeys was established to evaluate the effects of linear-ordered collagen scaffold (LOCS) and LOCS combined with collagen binding neurotrophin-3 (CBD-NT3), which has been demonstrated to promote axonal regrowth and functional restoration in rodent models. [J Neurotrauma] Abstract

Extracellular Matrix Remodeling Induced by Alternating Electrical and Mechanical Stimulations Increases the Contraction of Engineered Skeletal Muscle Tissues

ECM remodeling improved contractile force in a short time, and a coordinated, combined electrical and mechanical stimulation induced the desired ECM remodeling. Notably, the application of single and combined stimulations to engineered muscles remodeled the structure of their ECM networks, which determines the mechanical properties of the ECM. [Sci Rep] Full Article

Brain-Stiffness-Mimicking Tilapia Collagen Gel Promotes the Induction of Dorsal Cortical Neurons from Human Pluripotent Stem Cells

Researchers established a culture substrate that reproduced the stiffness of brain tissue using tilapia collagen for in vitro reconstitution assays. By adding crosslinkers, they obtained gels that were similar in stiffness to living brain tissue. [Sci Rep] Full Article

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Hyaluronan Biology: A Complex Balancing Act of Structure, Function, Location and Context

Investigators highlight the different, but inter-related factors that dictate biological activity of hyaluronan and introduce the overarching themes that weave through this special issue of Matrix Biology on hyaluronan. [Matrix Biol] Abstract

Biological Heterogeneity and Versatility of Cancer-Associated Fibroblasts in the Tumor Microenvironment

The authors summarize the latest knowledge regarding cancer-associated fibroblast (CAF) heterogeneity and offer a novel perspective and a beneficial approach for obtaining an improved understanding of CAFs. [Oncogene] Abstract

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

Aesculap Biologics, LLC Reaches Halfway Mark for Enrollment in Pivotal Phase III Clinical Trial of NOVOCART^® 3D in Patients with Articular Cartilage Defects of the Knee

Aesculap Biologics, LLC announced that it has successfully achieved 50 percent enrollment in the ongoing Phase III clinical trial of NOVOCART 3D, an autologous chondrocyte transplantation system designed to treat articular cartilage defects of the knee. [Aesculap Biologics, LLC] Press Release

Medtronic Announces Approval and Launch of Japan’s First DBM Bone Grafting Product for Spine and Orthopedic Procedures

Medtronic plc announced the Japanese launch of the Grafton^™ Demineralized Bone Matrix (DBM) bone grafting product for spine and orthopedic procedures. Grafton DBM is the first and only demineralized bone matrix product available in Japan, the world’s second largest market for spinal medical devices. [Medtronic plc (GlobeNewswire, Inc.)] Press Release

Big Pharma Is Embracing Open-Access Publishing Like Never Before

In a literature analysis, researchers found that the proportion of open-access papers published by 23 large drug companies, such as Pfizer and Roche, almost doubled between 2009 and 2016, and has overtaken the proportion of freely available papers published generally in medicine-related fields. [Nature News] Editorial

Spanish Science Reforms Aim to Make Life Easier for Parents

The Spanish government has passed reforms to the nation’s scientific system that will cut red tape and make life easier for researchers — especially parents. The reforms make it easier for public research institutions to hire staff, and for scientists to buy equipment and return to a science career after taking a maternity or paternity leave. [Nature News] Editorial

NIH Apologizes for Its Failure to Address Sexual Harassment in Science

The National Institutes of Health (NIH) apologized for its past failures to recognize and address the culture of sexual harassment that has impacted scientists for generations. “To all those who have endured these experiences, we are sorry that it has taken so long to acknowledge and address the climate and culture that has caused such harm,” NIH Director Francis Collins said in a statement. [STAT News] Editorial

NEW Gordon Research Conference: Cell Contact & Adhesion
June 2-7, 2019
Les Diablerets, Switzerland

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

NEW Assistant Professor – Sarcoma or Skeletal Related Malignancies (University of California at Davis)

Scientist – Matrix Biology (STEMCELL Technologies Inc.)

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

Tenure Track Professor Position – Architectured Biomedical Materials for Tissue Regeneration (Charite Universitatsmedizin Berlin)

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

Assistant Professor – Development & Re-Generation of Biological Systems (ETH Zurich)

Tenure Track Associate Professor – Molecular Cell Biology (Aarhus University)

Tenure Track Assistant Professor – Regenerative Medicine (University of British Columbia)

Associate Senior Lecturer – Molecular Medicine/Regenerative Medicine (Lund University)

Postdoctoral Associate – Planar Cell Polarity (Stony Brook University)

Postdoctoral Fellowship – Tissue Fibrosis Resolution (UCSF Cardiovascular Research Institute)

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