Muscle Cell News Volume 4.00 | Jan 7 2019

TOP STORY

Aggregation of Child Cardiac Progenitor Cells into Spheres Activates Notch Signaling and Improves Treatment of Right Ventricular Heart Failure

Cardiac progenitor cell (CPC) aggregation significantly increased gene expression of Notch1 compared to 2D CPCs, accompanied by significant upregulation of cardiogenic transcription factors and endothelial markers. Blocking Notch receptor activation with the γ-secretase inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester diminished these effects. [Circ Res] Abstract

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CARDIAC MUSCLE CELLS

LAMP-2B Regulates Human Cardiomyocyte Function by Mediating Autophagosome-Lysosome Fusion

Cardiomyocytes derived from induced pluripotent stem cells (hiPSC-CMs) from Danon patients exhibited decreased colocalization between ATG14 and VAMP8, profound defects in autophagic fusion, as well as mitochondrial and contractile abnormalities. This phenotype was recapitulated by lysosomal-associated membrane protein 2 isoform B (LAMP-2B) knockout in non-Danon hiPSC-CMs. [Proc Natl Acad Sci USA] Abstract

Decreased α-Tubulin Acetylation Induced by an Acidic Environment Impairs Autophagosome Formation and Leads to Rat Cardiomyocyte Injury

Investigators found that acidic environments inhibited autophagosome formation in cardiomyocytes. Up-regulation of autophagic activity, however, ameliorated the cell injury induced by acidic treatments. [J Mol Cell Cardiol] Abstract

Rare Mutations of ADAM17 from TOFs Induce Hypertrophy in Human Embryonic Stem Cell-Derived Cardiomyocytes via HB-EGF Signaling

Point mutation knock-in (KI) and ADAM17 KO human embryonic stem cells (hESCs) were generated by CRISPR/Cas9 and programmed to differentiate into cardiomyocytes (CMs). Researchers showed that PI3K/Akt, which is down stream of EGFR signaling, was affected in both ADAM17 KO and KI hESC-CMs. They showed that these two mutations are loss-of-function mutations in shedding HB-EGF but not NOTCH signaling. [Clin Sci (Lond)] Abstract | Full Article

SKELETAL MUSCLE CELLS

Engineering an Environment for the Study of Fibrosis: A 3D Human Muscle Model with Endothelium Specificity and Endomysium

Researchers demonstrated the induction of muscle-specific endothelium and the self-organization of endomysial muscle fibroblasts mediated by endothelial cells. They used the model to mimic the fibrotic environment characterizing muscular dystrophies and to highlight key signatures of fibrosis that are neglected or underestimated in traditional 2D monocultures. [Cell Rep] Full Article | Graphical Abstract

Liquid Crystal-Induced Myoblast Alignment

By using smooth polymeric films with planar homogeneous alignment, a certain degree of cellular order was observed in myoblast cultures with direction of higher cell alignment corresponding to the nematic director. The molecular organization inside the polymer determined such effects since no cell organization was observed using homeotropic or isotropic samples. [Adv Healthc Mater] Abstract

Astaxanthin but Not Quercetin Preserves Mitochondrial Integrity and Function, Ameliorates Oxidative Stress, and Reduces Heat-Induced Skeletal Muscle Injury

Scientists tested whether either astaxanthin or quercetin, two dietary antioxidants, could ameliorate heat-induced skeletal muscle oxidative injury. They also isolated rat flexor digitorum brevis myofibers and confirmed the data from C2C12 myoblasts that astaxanthin but not quercetin preserved mitochondrial integrity and function and ameliorated heat-induced skeletal muscle injury. [J Cell Physiol] Abstract

SMOOTH MUSCLE CELLS

The G-Protein Coupled Receptor ChemR23 Determines Smooth Muscle Cell Phenotypic Switching to Enhance High Phosphate-Induced Vascular Calcification

ChemR23-deficient smooth muscle cells maintained a non-synthetic phenotype and exhibited resistance to phosphate-induced calcification. Moreover, ChemR23-deficient mice were protected against vitamin D3-induced vascular calcification. [Cardiovasc Res] Abstract

Expression of a Functional IL-2 Receptor in Vascular Smooth Muscle Cells

Scientists report that vascular smooth muscle cells expressed all three subunits of IL-2R, and that expression of IL-2Rα varied with vascular smooth muscle cell phenotype. Furthermore, they showed that, through a functional IL-2R, IL-2 initiated signaling pathways and impacted vascular smooth muscle cell function. [J Immunol] Abstract

Hyperglycemia Induces Vascular Smooth Muscle Cell Dedifferentiation by Suppressing Insulin Receptor Substrate-1-Mediated p53/KLF4 Complex Stabilization

Researchers sought to define the mechanism by which insulin receptor substrate-1 (IRS-1) maintains vascular smooth muscle cell differentiation. IRS-1 overexpression in high glucose inhibited the MDM2/p53 association, leading to increased p53 and p53/krüppel-like factor 4 (KLF4) levels thereby increasing differentiation. [J Biol Chem] Abstract | Full Article

RING Finger Protein 10 Attenuates Vascular Restenosis by Inhibiting Vascular Smooth Muscle Cell Hyperproliferation In Vivo and Vitro

Investigators found that overexpression of RING finger protein 10 significantly affected neointima formation and vascular smooth muscle cell proliferation, and displayed further inhibitory activity by promoting mesenchyme homeobox 2 and suppressing activating protein 1. [IUBMB Life] Abstract

Hypoxia-Induced ARHGAP26 Deficiency Inhibits the Proliferation and Migration of Human Ductus Arteriosus Smooth Muscle Cell through Activating RhoA-ROCK-PTEN Pathway

Human ductus arteriosus (DA) smooth muscle cells (DASMCs) were isolated and cultured in vitro and used to test the function of rho GTPase-activating protein 26 (ARHGAP26). ARHGAP26-knocked-down human DASMCs showed reduced proliferation and migration, which are both crucial to anatomic closure of DA. [J Cell Biochem] Abstract

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Skeletal Muscle Stem Cells in Comfort and Stress

The authors discuss heterogeneities among muscle stem cells and how distinct properties within the quiescent and proliferating cell states might impact on homoeostasis and regeneration. These and other factors including metabolic activity and genetic background can impact the efficiency of muscle regeneration. [NPJ Regen Med] Full Article

Visit our reviews page to see a complete list of reviews in the muscle cell research field.

MyoKardia Regains Global Rights to Mavacamten and MYK-491 Programs from Sanofi

MyoKardia, Inc. announced it has regained worldwide rights to all programs covered under its license and collaboration agreement with Sanofi. The collaboration will not be extended beyond the initial research term, which ended on December 31, 2018, and will conclude in its entirety effective April 1, 2019. [MyoKardia, Inc.] Press Release

Catabasis Pharmaceuticals Phase III PolarisDMD Clinical Trial for Edasalonexent in Duchenne Muscular Dystrophy Progress Update and Additional Trial Sites Open for Enrollment

Catabasis Pharmaceuticals, Inc. shared an update on clinical trial sites in the United States and recent international clinical trial application approvals to perform the Phase III PolarisDMD trial for edasalonexent in Duchenne muscular dystrophy. PolarisDMD clinical trial sites in the United States are actively enrolling patients. [Catabasis Pharmaceuticals, Inc.] Press Release

Phase III Trial of Mesoblast’s Cell Therapy in Chronic Heart Failure Completes Recruitment

Mesoblast Limited announced that it has completed patient recruitment in the events-driven Phase III trial of its product candidate Revascor for advanced chronic heart failure. [Mesoblast Limited (GlobeNewswire, Inc.)] Press Release

Wave Life Sciences Duchenne Muscular Dystrophy Clinical Trial Selected for FDA Complex Innovative Trial Designs Pilot Program

Wave Life Sciences Ltd. announced that the planned Phase II/III efficacy and safety trial for its lead Duchenne muscular dystrophy clinical program has been selected for the FDA pilot program for complex innovative trial designs (CID). This marks the first time that the FDA has selected clinical protocols for its CID pilot program that was announced in August 2018. [Wave Life Sciences] Press Release

Myonexus Therapeutics Receives Orphan Drug Designation for MYO-102, an Investigational Gene Therapy for Alpha-Sarcoglycanopathy (LGMD2D)

Myonexus Therapeutics, announced that the FDA has granted Orphan Drug Designation for MYO-102, a novel gene therapy candidate for alpha-sarcoglycanopathy, also known as Limb Girdle Muscular Dystrophy Type 2D (LGMD2D). [Myonexus Therapeutics] Press Release

Sarepta Therapeutics Completes Submission of New Drug Application Seeking Approval of Golodirsen (SRP-4053) in Patients with Duchenne Muscular Dystrophy Amenable to Skipping Exon 53

Sarepta Therapeutics, Inc. announced that it has completed the submission of its rolling New Drug Application seeking accelerated approval for golodirsen, a phosphordiamidate morpholino oligimer engineered to treat those patients with Duchenne muscular dystrophy who have genetic mutations subject to skipping exon 53 of the Duchenne gene. [Sarepta Therapeutics, Inc.] Press Release

Funding for the Development of New Gene Therapies for Cardiovascular Diseases

Faculty of Medicine and University Medical Center Schleswig-Holstein Kiel receive 1.4 million euros research funding from the EU. The aim is to develop new and more efficient treatment approaches for cardiovascular diseases. The project will be funded from January 2019 for a period of five years, through the EU research framework program “Horizon 2020”. [Kiel University] Press Release

BMC Biology Shares Rejected Papers’ Peer Reviews with Other Journals

The Springer Nature journal BMC Biology plans to provide rival publications with peer reviews of papers it rejects. BMC Biology aims to cut down on wasted time in the peer-review process by providing these reviews for reuse, for instance, when the manuscript did not fit the scope of the publication. [The Scientist] Editorial

UK Universities Warn ‘No Deal’ Brexit Will Hit Crucial Funding Streams

UK universities have warned the country’s government that leaving the European Union without a deal is “one of the biggest threats” the institutions have ever faced. Britain is scheduled to leave the EU on 29 March, but a deal on the terms of its departure is yet to be fully agreed. Members of the UK Parliament are expected to vote on a proposed deal later this month. [Nature News] Editorial

Scientists Despair as US Government Shutdown Drags On

Space missions can continue to collect data, but thousands of federal researchers are forced to stay at home without pay. As the shutdown hits the two-week mark with no end in sight, its effects on science have begun to compound, leaving many government researchers weary, worried and demoralized. [Nature News] Editorial

NEW 2^nd International Translational & Regenerative Medicine Conference
April 15-16, 2019
Valencia, Spain

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

NEW Assistant Professor – Sarcoma & Skeletal-Related Malignancies (UC Davis School of Medicine)

NEW Scientist – Myotonic Dystrophy Type 1 Drug Discovery (Expansion Therapeutics, Inc.)

NEW Professor – Cardiovascular Research (The University of Tennessee Health Science Center)

Assistant Professor Positions – Department of Cardiology (Boston Children’s Hospital)

Tenure Track Assistant Professor – Molecular Mechanisms of Muscles for Exercise & Health (Technical University of Munich)

Postdoctoral Fellowship – Cardiovascular Sciences (Medical College of Wisconsin)

Postdoctoral Researcher – Muscle Regeneration & Muscular Dystrophy Research (Carnegie Institution of Science)

Postdoctoral Research Fellow – Sarcopenia (Lee Kong Chian School of Medicine)

Assistant/Associate Adjunct Professor – Cardiovascular Medicine (UC Davis)

Postdoctoral Research Fellow – Cardiac RNA Biology (University of Illinois at Chicago)

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