Mesenchymal Cell News Volume 10.27 | Jul 10 2018

TOP STORY

Efficient Gene Transfer to Kidney Mesenchymal Cells Using a Synthetic Adeno-Associated Viral Vector

Of the six adeno-associated viruses (AAVs) tested, a synthetic AAV called Anc80 showed specific and high-efficiency transduction of kidney stroma and mesangial cells. Investigators characterized the cell specificity, dose dependence, and expression kinetics and showed the efficacy of this approach by knocking out Gli2 from kidney mesenchymal cells by injection of Anc80-Cre virus into either homozygous or heterozygous Gli2-floxed mice. [J Am Soc Nephrol] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

IN VITRO

Notch-Inducing Hydrogels Reveal a Perivascular Switch of Mesenchymal Stem Cell Fate

Scientists studied MSCs in the perivascular microenvironment of endothelial capillaries by modifying a synthetic 3D biomimetic poly(ethylene glycol)-hydrogel system in vitro. Transcriptome analysis of human MSCs isolated from engineered capillaries showed a prominent switch in extracellular matrix (ECM) production. Transient culture of MSCs in Notch-inducing microenvironments revealed the reversibility of this ECM switch. [EMBO Rep] Abstract | Graphical Abstract

Injectable Degradable PVA Microgels Prepared by Microfluidic Technology for Controlled Osteogenic Differentiation of Mesenchymal Stem Cells

Human MSCs (hMSCs) sustained high viability in poly(vinyl alcohol) (PVA) microgels, and cell proliferation and migration behaviors could easily be adjusted by varying crosslinking densities of PVA microgels. Additionally, bone morphogenetic protein-2 co-encapsulated into the microgel environments enhanced osteogenic differentiation of hMSCs as indicated by a significant increase in alkaline phosphatase activity, calcium content, and Runx2 and OPN gene expression levels. [Acta Biomater] Abstract | Graphical Abstract

A Novel Phosphorylation by AMP-Activated Kinase Regulates RUNX2 from Ubiquitination in Osteogenesis over Adipogenesis

Researchers showed for the first time that RUNX2 is a novel substrate of AMP-activated kinase (AMPK), which directly phosphorylated at serine 118 residue in the DNA-binding domain of RUNX2. Their results in in vitro MSC lineage differentiation models confirmed that active AMPK and RUNX2-S118 phosphorylation were preferentially associated with osteogenic commitment, whereas the lack of this phosphorylation lead to adipogenesis. [Cell Death Dis] Full Article

Plastrum Testudinis Extracts Promote BMSC Proliferation and Osteogenic Differentiation by Regulating Let-7f-5p and the TNFR2/PI3K/AKT Signaling Pathway

Plastrum testudinis extracts (PTE) significantly promoted bone marrow MSC (BMSC) osteogenic differentiation and mineralization after 7 and 14 days in culture, respectively. The combination of PTE and osteogenic induction exhibited significant synergy. PTE upregulated Let-7f-5p, β-catenin, Runx2, and Ocn mRNA expression, and downregulated Tnfr2, Traf2, Pi3k, Akt, and Gsk3β mRNA expression. [Cell Physiol Biochem] Full Article

IN VIVO

HMGA1/E2F1 Axis and NFkB Pathways Regulate LPS Progression and Trabectedin Resistance

The in vitro and in vivo treatment of myxoid liposarcoma with trabectedin, a drug with a potent anti-tumor activity, revealed downregulation of HMGA1, E2F1, and its-downstream targets, vimentin and ZEB1, indicating a critical role of trabectedin in inhibiting the mesenchymal markers of these tumors through the HMGA1/E2F1 axis. Trabectedin treatment inhibited in vitro NFkB pathway in mixoyd liposarcoma sensitive but not in resistant counterparts, and the inhibition of NFkB pathway re-sensitized the resistant cells to trabectedin treatment. [Oncogene] Full Article

Hypoxic Preconditioning of Mesenchymal Stem Cells with Subsequent Spheroid Formation Accelerates Repair of Segmental Bone Defects

Human MSCs were preconditioned in 1% O₂ in monolayer culture for 3 days or kept in ambient air, formed into spheroids of increasing cell density, and then entrapped in alginate hydrogels. Hypoxia-preconditioned MSC spheroids were more resistant to apoptosis than ambient air controls and this response correlated with duration of hypoxia exposure. Spheroid-containing gels induced significantly more bone healing compared with gels containing preconditioned individual MSCs or acellular gels. [Stem Cells] Abstract | Full Article | Press Release

Therapeutic Effect of Dental Pulp Stem Cell Transplantation on a Rat Model of Radioactivity-Induced Esophageal Injury

In the injured esophagus, PKH26-labeled dental pulp stem cells (DPSCs) co-localized with PCNA, CK14, CD71, and integrin α6, and the expression levels of these four makers of esophageal stem cells were significantly increased. After DPSC transplantation, the injured esophagus exhibited a greater thickness. In addition, the esophageal function and inflammation recovered faster. [Cell Death Dis] Full Article

Syndecan-2-Positive, Bone Marrow-Derived Human Mesenchymal Stromal Cells Attenuate Bacterial-Induced Acute Lung Injury and Enhance Resolution of Ventilator-Induced Lung Injury in Rats

In vitro studies determined whether CD362 human MSCs could modulate pulmonary epithelial inflammation, wound healing, and macrophage phagocytosis. Two in vivo rodent studies determined whether CD362 human MSCs attenuated Escherichia coli-induced lung injury and enhanced resolution of ventilation-induced injury. [Anesthesiology] Abstract

DEPTOR Regulates Osteogenic Differentiation via Inhibiting MEG3-Mediated Activation of BMP4 Signaling and is Involved in Osteoporosis

The expression of DEP domain containing mammalian target of rapamycin interacting protein (DEPTOR) was reduced during the osteogenic differentiation of bone marrow MSCs (BMSCs), and knockdown of DEPTOR promoted BMSC osteogenesis in vitro and in vivo. Long noncoding RNA and mRNA sequences indicated that knockdown of DEPTOR upregulated the expression of maternally expressed 3 (nonprotein coding) (MEG3), which subsequently activated bone morphogenetic protein 4 (BMP4) signaling. [Stem Cell Res Ther] Full Article

Human Mesenchymal Stromal Cells Inhibit Platelet Activation and Aggregation Involving CD73-Converted Adenosine

Bone marrow (BM)-MSCs and lipoaspirate (LA)-MSCs inhibited activation and aggregation of stimulated platelets independent of the agonist used. Using inhibitors of the CD39–CD73–adenosine axis, investigators showed that adenosine produced by CD73 ectonucleotidase activity was largely responsible for the LA-MSC and BM-MSC platelet inhibitory action. [Stem Cell Res Ther] Full Article

Subscribe to one of our other 19 science newsletters such as ESC & iPSC News & Cell Therapy News.

Ewing Sarcoma

Ewing sarcoma is the second most frequent bone tumor of childhood and adolescence that can also arise in soft tissue. Ewing sarcomas are composed of small round cells expressing high levels of CD99. Emerging studies on the molecular mechanisms of Ewing sarcoma hold promise for improvements in early detection, disease monitoring, lower treatment-related toxicity, overall survival and quality of life. [Nat Rev Dis Primers] Abstract

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

Major Lupus Stem Cell Study Receives Additional Funding from the National Institutes of Health

The Lupus Foundation of America announced the launch of a new public-private partnership with the National Institute of Allergy and Infectious Diseases to co-fund a major Phase II study to evaluate MSCs as a treatment for moderate to severe lupus. [Lupus Foundation of America, Inc.] Press Release

BrainStorm Granted Japanese Patent for NurOwn^®

BrainStorm Cell Therapeutics Inc. announced that it has received a Decision to Grant notice from the Japanese Patent Office to issue a patent entitled: “Methods of generating mesenchymal stem cells which secrete neurotrophic factors.” [BrainStorm Cell Therapeutics Inc.] Press Release

Cellectar’s CLR 131 Receives FDA Orphan Drug Designation for Treatment of Ewing’s Sarcoma

Cellectar Biosciences announced that the FDA Office of Orphan Products Development has granted Orphan Drug Designation to CLR 131, the company’s lead Phospholipid Drug Conjugate^™ product candidate, for the treatment of Ewing’s sarcoma. [Cellectar Biosciences, Inc.] Press Release

Report Advocates Broader Return of Research Results

A 335-page report from the National Academies of Sciences, Engineering, and Medicine urges researchers and regulators to return more biological data to the people whose samples yielded it in the first place. [ScienceInsider] Editorial

New Scheme for Overseas Researchers to Come to the UK

The new ‘UKRI Science, Research and Academia’ scheme, which allows non-EEA researchers, scientists and academics to come to the UK for up to 2 years, opened on Friday 6 July, the Immigration Minister announced. The new scheme, which is being added to the Tier 5 visa route, has been introduced to reflect and encourage the ongoing growth of the research sector in the UK. [UK Visas and Immigration] Editorial

NEW The 3^rd Conference on Tissue Engineering and Regenerative Medicine (CTERM 2019)
January 5-7, 2019
Sanya, China

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

NEW Postdoctoral Position – Regenerative Biology (Helmholtz Zentrum München – German Research Center for Environmental Health)

Senior Lecturer – Stromal Immunology (University of Aberdeen)

Research Assistant – Synthetic Scaffolds for Tendon Repair (University of Oxford)

Postdoctoral Research Fellows – Tissue Morphogenesis (Max-Planck-Institute for Molecular Biomedicine)

Postdoctoral Fellowship – DNA Damage Repair and Pediatric Sarcoma Therapy (UT Health Science Center at San Antonio)

NEW Faculty Position – Cellular Physiology and Engineering (Mayo Clinic)

Postdoctoral Research Assistant – Stem Cell Based Regenerative Medicine (Queen Mary University of London)

Research Fellow – Stem Cell Biology and Engineering (New York Blood Center)

Research Assistant – Cell Culture and Engineering (University of Oxford)

Experimental Postdoctoral Position – Single-Cell Functional Genomics (Heidelberg University)

Postdoctoral Positions – Cell Biology (Children’s Hospital of Philadelphia)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Mesenchymal Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.