Mesenchymal Cell News Volume 11.42 | Oct 29 2019

TOP STORY

Mycobacterium tuberculosis Programs Mesenchymal Stem Cells to Establish Dormancy and Persistence

Researchers showed that Mycobacterium tuberculosis (M. tb) was taken up by MSCs, where it established dormancy and became highly non-responsive to isoniazid, a major constituent of Directly Observed Treatment Short-course. Dormant M.tb induced quiescence in MSCs and promoted their long-term survival. [J Clin Invest] Abstract

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IN VITRO

Tankyrase Inhibition Preserves Osteoarthritic Cartilage by Coordinating Cartilage Matrix Anabolism via Effects on SOX9 PARylation

Investigators reported the identification of tankyrase as a regulator of the cartilage anabolism axis based on systems-level factor analysis of mouse reference populations. Tankyrase inhibition drove the expression of a cartilage-signature matrisome and elicited a transcriptomic pattern that was inversely correlated with osteoarthritis progression. [Nat Commun] Full Article

Disruption of Gap Junctions Attenuates Acute Myeloid Leukemia Chemoresistance Induced by Bone Marrow Mesenchymal Stromal Cells

The comparison of bone marrow (BM)-MSCs from acute myeloid leukemia (AML) patients and healthy donors revealed a specific profile of connexins in BM-MSCs of the leukemic niche and the effects of carbenoxolone (CBX), a gap junction disruptor, were evaluated on AML cells. CBX presented an antileukemic effect without affecting normal BM-CD34⁺ progenitor cells. [Oncogene] Full Article

SPRY4 Is Responsible for Pathogenesis of Adolescent Idiopathic Scoliosis by Contributing to Osteogenic Differentiation and Melatonin Response of Bone Marrow-Derived Mesenchymal Stem Cells

The authors focused on one of the most downregulated genes, SPRY4, in the MAPK signaling pathway and examined its role in osteogenic differentiation. They found that SPRY4 was markedly down-regulated in AIS MSCs. Knockdown of SPRY4 impaired differentiation of healthy MSCs to osteoblasts, while SPRY4 over-expression in adolescent idiopathic scoliosis MSCs enhanced osteogenic differentiation. [Cell Death Dis] Full Article

Tunable Hydrogels for Mesenchymal Stem Cell Delivery: Integrin-Induced Transcriptome Alterations and Hydrogel Optimization for Human Wound Healing

Researchers synthesized cell-degradable hydrogels based on bio-inert poly(ethylene glycol) tethered with specific integrin-binding small molecules and have characterized their resulting effect on the MSC transcriptome when compared to 2D cultured and untethered 3D hydrogel cultured MSCs. [Stem Cells] Abstract

Central Metabolism of Functionally Heterogeneous Mesenchymal Stromal Cells

Human (h)MSC were shown to possess significantly distinct proliferation rate, senescence status and differentiation capacity. More potential hMSC were associated to higher mitochondrial DNA copy number and lower mtDNA methylation. [Sci Rep] Full Article

Precise Immunomodulation of the M1 to M2 Macrophage Transition Enhances Mesenchymal Stem Cell Osteogenesis and Differs by Sex

A primary murine macrophage-MSC co-culture system was used to demonstrate the optimal transition time from M1 to M2 macrophages to maximize matrix mineralization in male and female MSCs. Outcome variables included Alizarin Red staining, alkaline phosphatase activity, and osteocalcin protein secretion. [Bone Joint Res] Full Article

Study of the Protective Effect on Damaged Intestinal Epithelial Cells of Rat Multilineage-Differentiating Stress-Enduring (Muse) Cells

Rat Muse cells were separated from bone-marrow (BM) MSCs by trypsin-incubation stress. The group of cells maintained the characteristics of BMMSCs; however, there were high positive expression levels of stage-specific embryonic antigen-3 and stage-specific embryonic antigen-1, as well as specific antigens including nanog, POU class 5 homeobox 1, and SRY-box 2. [Cell Biol Int] Full Article

IN VIVO

Human iPSC-Derived iMSCs Improve Bone Regeneration in Mini-Pigs

Induced MSCs were derived from induced pluripotent stem cells originating from human fetal foreskin fibroblasts. They were able to differentiate into osteoblasts in vitro, expressed a plethora of bone morphogenic proteins and secreted paracrine signaling-associated cytokines such as PDGF-AA and osteopontin. [Bone Res] Full Article

PROTAC Induced-BET Protein Degradation Exhibits Potent Anti-Osteosarcoma Activity by Triggering Apoptosis

Scientists investigated the in vitro and in vivo anti-osteosarcoma activity by targeting bromodomain and extra-terminal (BET) with a proteolysis-targeting chimera (PROTAC) molecule BETd-260. The results showed that BETd-260 completely depleted BET proteins and potently suppressed cell viability in MNNG/HOS, Saos-2, MG-63, and SJSA-1 osteosarcoma cell lines. [Cell Death Dis] Full Article

Long Noncoding RNA CEBPA-AS1 Overexpression Inhibits Proliferation and Migration and Stimulates Apoptosis of Osteosarcoma Cells via the Notch Signaling Pathway by MicroRN-10b-5p-Mediated NCOR2

Microarray-based expression analysis identified osteosarcoma (OS)-related differentially expressed lncRNA, and predicted microRNAs binding to lncRNA and mRNA. LncRNA CEBPA-AS1 and NCOR2 were found to be weakly expressed in OS tissues and cells. Functional investigation revealed that lncRNA CEBPA-AS1 bound to miR-10b-5p to up-regulate NCOR2. [Mol Ther Nucleic Acids] Abstract | Graphical Abstract

Modeling Snyder-Robinson Syndrome in Multipotent Stromal Cells Reveals Impaired Mitochondrial Function as a Potential Cause for Deficient Osteogenesis

Researchers found that silencing spermidine synthase (SMS) in MSCs led to reduced cell proliferation and deficient bone formation in vitro, as evidenced by reduced mineralization and decreased bone sialoprotein expression. Furthermore, transplantation of MSCs in osteoconductive scaffolds into immune deficient mice showed that silencing SMS also reduced ectopic bone formation in vivo. [Sci Rep] Full Article

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The Application of Resveratrol to Mesenchymal Stromal Cell-Based Regenerative Medicine

The authors concluded that resveratrol (RSV) significantly improved the preventive and therapeutic effects of MSCs against multiple diseases. They also describe the underlying mechanisms of the effects of RSV on the survival, self-renewal, and lineage commitment of MSCs in vitro and in vivo. [Stem Cell Res Ther] Full Article

The Potential of Mesenchymal Stem Cell Therapy for Chronic Lung Disease

Investigators covered rationale for the use of MSC therapy, along with preclinical studies and clinical trials with MSC therapy in chronic lung diseases. Expert opinion: MSC therapy holds promise for the treatment of chronic lung diseases, mainly when administered at early stages. [Expert Rev Respir Med] Abstract

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NurOwn^® Data Safety Monitoring Board Recommends ALS Phase III Clinical Trial Continue

BrainStorm Cell Therapeutics, Inc. announced that the Phase III clinical trial independent Data Safety Monitoring Board has completed the second, pre-specified interim analysis, of safety outcomes for the first 106 patients who received repeat dosing of NurOwn^® in the Phase III trial for ALS patients. [BrainStorm Cell Therapeutics, Inc.] Press Release

Florida Tech to Build $18M Health Sciences Research Center

Florida Institute of Technology will break ground in spring 2020 on a 61,000-square-foot Health Sciences Research Center that will help fill the growing demand for jobs in biomedical engineering and science and allow students and faculty to conduct critical research in labs equipped with the latest cutting-edge technologies, from virtual-dissection tables to atomic force microscopes. [Florida Institute of Technology] Press Release

UCL to Phase Out Single-Use Plastics, Including Pipette Tips

University College London made a series of pledges last week to cut down on plastic waste, help mitigate climate change, and make its research and teaching facilities more environmentally sustainable. If all goes to plan, UCL will divest from fossil fuel-producing companies by the end of this year, have one and a half football pitches’ worth of green space on its campus within five years, and offer vegetarian options only through its catering and hospitality services by 2030. [The Scientist] Editorial

Argentine Scientists Rally Behind Favorite in Sunday’s Presidential Election

Thousands of Argentine scientists are hoping the man expected to be the country’s next president will reverse deep cuts to research imposed by the conservative government of President Mauricio Macri. But the first priority for Alberto Fernández, the front-runner in October 27^th‘s election, will almost certainly be Argentina’s crumbling economy. And it’s not clear when- or how effectively- the concerns of scientists will be addressed. [ScienceInsider] Editorial

German University Finds ‘Severe’ Misconduct by Researcher Who Promoted Questionable Cancer Blood Test

A university commission announced this week it had found evidence of “extensive and severe scientific misconduct” by Christof Sohn, director of the women’s clinic at Heidelberg University Hospital in Germany and the lead researcher behind a highly publicized but questionable blood test designed to detect breast cancer. [ScienceInsider] Editorial

NEW The Life of the Skeleton from Embryonic Development to Aging
February 2-7, 2020
Galveston, Texas, United States

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NEW Faculty Position – Regenerative Medicine and Tissue Engineering (Columbia University)

NEW Research Assistant – Stem Cells and Engineering (New York Blood Center)

Researcher – Biomaterials and Stem Cells (National University of Ireland Galway)

Postdoctroal Researcher – CRISPR/Cas9 in Tissue Regeneration (Howard Hughes Medical Institute)

Tenure-Track Positions – Biologic and Materials Sciences & Prosthodontics (University of Michigan)

Professor Positions – Biomedical Science (The Chinese University of Hong Kong)

Assistant Professor – Cell and Molecular Biology (Boston University)

Postdoctoral Researcher – Stem Cells (University of South Florida)

Postdoctoral Fellow – Stem Cells (The Francis Crick Institute)

Postdoctoral Researcher – Proteoglycans in Post-Traumatic Osteoarthritis (Drexel University)

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