Mesenchymal Cell News Volume 11.27 | Jul 16 2019

TOP STORY

Regulation of Tumor Angiogenesis and Mesenchymal-Endothelial Transition by p38α through TGF-β and JNK Signaling

Researchers showed that p38α negatively regulated an angiogenic program in mesenchymal stem/stromal cells (MSCs), multipotent progenitors found in perivascular locations. This program included the acquisition of an endothelial phenotype by MSCs mediated by both TGF-β and JNK, and negatively regulated by p38α. [Nat Commun] Full Article | Press Release

(Ranked by impact factor of the journal)

IN VITRO

Mesenchymal Stromal Cells Confer Chemoresistance to Myeloid Leukemia Blasts through Side Population Functionality and ABC Transporter Activation

Scientists demonstrated that contact with mesenchymal stromal cells promoted a better survival of blasts in culture in the presence of anthracycline through the activation of ABC transporters. Stroma-dependent ABC transporter activation led to the induction of a side population phenotype in a subpopulation of primary leukemia blasts through Alpha4 engagement. [Haematologica] Abstract

Mesenchymal Stem Cell-Mediated Delivery of an Oncolytic Adenovirus Enhances Antitumor Efficacy in Hepatocellular Carcinoma

The authors showed that MSCs could be effectively infected by hepatocellular carcinoma (HCC)-oncolytic adenovirus (oAd) through modification of the virus’ fiber domain and that the virus replicated efficiently in the cell carrier. HCC-targeting oAd loaded in MSCs effectively lysed HCC cells in vitro under both normoxic and hypoxic conditions as a result of the hypoxia responsiveness of HCC-oAd. [Cancer Res] Abstract

Functional Secretome Analysis Reveals Annexin-A1 as Important Paracrine Factor Derived from Fetal Mesenchymal Stem Cells in Hepatic Regeneration

The anti-inflammatory molecule annexin-A1 (ANXA1) was detected at high levels in both the amniotic fluid-MSC and the hepatic progenitor-like (HPL) cell secretome. Further functional analyses revealed that the shRNA-mediated knock-down of ANXA1 in MSCs decreased their proliferative, clonogenic and migratory potential, as well as their ability to differentiate into HPL cells. [EBioMedicine] Full Article

Tunneling Nanotubes Mediate the Expression of Senescence Markers in Mesenchymal Stem/Stromal Cell Spheroids

Compared to spheroids formed solely of high passage MSCs, the addition of low passage MSCs reduced p16 expression, a known genetic marker of senescence. Researchers observed a significant increase in p16 expression in high passage cells when tunneling nanotube (TNT) formation was inhibited, establishing the importance of TNTs in MSC spheroids. [Stem Cells] Abstract

IN VIVO

Dual Stem Cell Therapy Synergistically Improves Cardiac Function and Vascular Regeneration following Myocardial Infarction

Epicardially implanted human MSC-loaded patch provided a complimentary microenvironment which enhanced vascular regeneration through prolonged secretion of paracrine factors, but more importantly it significantly improved the retention and engraftment of intramyocardially injected human induced pluripotent stem cells which ultimately restored cardiac function. [Nat Commun] Full Article

Programmable Microencapsulation for Enhanced Mesenchymal Stem Cell Persistence and Immunomodulation

Investigators demonstrated that biomaterial encapsulation into alginate using a microfluidic device could substantially increase in vivo MSC persistence after intravenous injection. A combination of cell cluster formation and subsequent cross-linking with polylysine led to an increase in injected MSC half-life by more than an order of magnitude. [Proc Natl Acad Sci USA] Abstract | Press Release

Combinatorial Targeting of Cancer Bone Metastasis Using mRNA Engineered Stem Cells

Researchers used MSCs engineered using mRNA to simultaneously express P-selectin glycoprotein ligand-1/Sialyl-Lewis X, and modified versions of cytosine deaminase and osteoprotegerin to target and treat breast cancer bone metastases in two mouse models, a xenograft intratibial model and a syngeneic model of spontaneous bone metastasis. [EBioMedicine] Full Article | Press Release

Transplantation of Aggregates of Autologous Synovial Mesenchymal Stem Cells for Treatment of Cartilage Defects in the Femoral Condyle and the Femoral Groove in Microminipigs

Scientists investigated whether transplantation of aggregates of autologous synovial MSCs with two-step surgery could promote articular cartilage regeneration in microminipig osteochondral defects. [Am J Sports Med] Abstract

C1q/Tumor Necrosis Factor-Related Protein-3-Engineered Mesenchymal Stromal Cells Attenuate Cardiac Impairment in Mice with Myocardial Infarction

Injection of MSCs or control virus-transfected MSCs improved the left ventricular ejection fraction, inhibited cardiac fibrosis, and regulated cellular profiles of the infarction border zone four weeks after myocardial infarction (MI) compared with those in the phosphate-buffered saline group. Furthermore, overexpression of h C1q/tumor necrosis factor-related protein-3 promoted the efficacy of MSCs in the treatment of MI. [Cell Death Dis] Full Article

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Surgical and Tissue Engineering Strategies for Articular Cartilage and Meniscus Repair

The authors provide a summary of surgical techniques, including tissue-engineered products, that are currently in clinical use, as well as a discussion of state-of-the-art tissue engineering strategies and technologies that are being developed for use in articular cartilage and meniscus repair and regeneration. [Nat Rev Rheumatol] Abstract

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Epistem Licence Hubrecht Organoid Technology to Expand Preclinical Toxicology Service Portfolio

Epistem Limited announced the expansion of its in vitro model portfolio by the completion of an agreement with Hubrecht Organoid Technology to enable the delivery of an increased range of multi species organoid models. Services are focused on the identification of off target or off tissue intestinal toxicities associated with various therapeutics. [Epistem Ltd.] Press Release

First Utahns Treated in Nationwide FDA-Allowed Clinical Study of Locally Developed Cell Therapy for Chronic Low Back Pain

DiscGenics, Inc. announced the first Utahns have been treated in its nationwide clinical study of IDCT, a locally developed injectable disc cell therapy for degenerative disc disease (DDD). The clinical study is designed to evaluate the safety and preliminary efficacy of IDCT, a homologous and allogeneic cell therapy, in the treatment of mild to moderate DDD. [DiscGenics, Inc.] Press Release

Engineering Faculty Member Receives Grants Totaling $1.5M for Bioprinting

Ibrahim Tarik Ozbolat, Hartz Family Career Development Associate Professor of Engineering Science and Mechanics, has received four grants totaling about $1.5 million to explore ways to bioprint biological tissues like bone, lungs and other organs for use as models in a variety of studies. [The Pennsylvania State University] Press Release

University of California Loses Access to New Journal Articles Published by Elsevier after Research Access Fight

Researchers in the University of California system lost subscription access to the major publisher Elsevier, the result of a closely watched fight between the two parties over how academic research should get read and paid for. [STAT News] Editorial

Sweden Passes Law For National Research Misconduct Agency

After several high-profile cases, the country’s government is creating a board to oversee and investigate all serious allegations of scientific misconduct. [The Scientist] Editorial

NEW Cell Symposia: Gene and Cell Based Therapies: CRISPR, Stem Cells & Beyond
March 2-4, 2020
San Francisco, California, United States

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NEW Assitant Director – Cell & Gene Therapy Laboratory (MD Anderson Cancer Center)

Associate Professor – Stem Cell Science (University College London)

Tenure-Track Position – Stem Cell Biology and Regenerative Medicine (Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellow – Mesenchymal Tumor Invasion Research (Luxembourg Institute of Health)

Assistant Director – Cell & Gene Therapy (MD Anderson Cancer Center)

Postdoctoral Fellow – Immunology & Respiratory Disease Research with MSCs (Boehringer Ingelheim)

Development Scientist – Cell Therapy (GE)

Postdoctoral Researchers – Cardiometabolic Diseases (Columbia University Medical Center)

Postdoctoral Fellow – MSCs in Skeletal Development (University of Pennsylvania)

Assistant Professor – Musculoseketal Biology (Keck School of Medicine of USC)

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