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Biology subjects

Moriyama, K.

Publications and source records attributed to Moriyama, K..

3 recordsLinked to original sources

Mesenchymal Stem Cell Membrane Coating of Gelatin Nanospheres with Drug Release Ability for Inflammatory Tissue Targeting

Improvements in drug delivery have been achieved using nanospheres to prolong drug efficacy, accelerate absorption, and target tissues with ongoing inflammation. Although nanospheres have numerous pharmacokinetic advantages their tissue-targeting ability is poor. In contrast, mesenchymal stem cells (MSC) accumulate in high numbers in inflammatory tissues via the interaction between CXC-chemokine receptor 4 (CXCR4) expressed on MSC and stromal cell-derived factor 1 (SDF-1) secreted during inflammation. Therefore, this study investigated coating gelatin nanospheres (GNS) with MSC membranes (MSC-GNS) by extrusion and ultrasonication methods to enhance their inflammatory tissue tropism. {zeta}-potential measurements, western blotting and single-particle analysis of MSC-GNS by flow cytometry demonstrated the GNS surface was successfully coated with MSC membranes. Dot blotting demonstrated the binding ability of CXCR4 for SDF-1 was retained by MSC-GNS but absent for MSC-membrane-free GNS. The blood clearance of MSC-GNS was examined by their intravenous injection into mice. Although MSC-GNS and GNS were retained during the early distribution phase, MSC-GNS had a higher retention than GNS during the later elimination phase. Finally, we investigated the tissue distribution of MSC-GNS by intravenous injection into a mouse model of liver fibrosis and their potential therapeutic effect on liver fibrosis. We found a higher accumulation of MSC-GNS in inflamed livers and higher blood retention compared with MSC-membrane-free GNS. Furthermore, MSC-GNS loaded with an anti-fibrotic agent (LSKL, a 4-amino acid peptide that inhibits fibrosis progression) had an enhanced therapeutic effect on liver fibrosis than uncoated nanoparticles. Therefore, MSC-GNS might be a drug carrier with inflammatory tissue targeting and controlled drug release abilities. Synopsis Table of Contents Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/657318v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@12331d8org.highwire.dtl.DTLVardef@19d7b43org.highwire.dtl.DTLVardef@79591org.highwire.dtl.DTLVardef@1ec805a_HPS_FORMAT_FIGEXP M_FIG C_FIG Mesenchymal stem cell membrane coated gelatin nanosphere as DDS nanocarrier

bioengineering↗

Nuclear activation in dual-durotaxing cells on a matrix with cell-scale stiffness-heterogeneity

Living organisms are typically composed of various tissues with microscopic cell-scale stiffness-heterogeneity, in which some cells receive dynamically fluctuating mechanical stimuli from the heterogeneous extracellular milieu during long-term movement. Although intracellular stress dynamics (ISD), which are closely related to the regulation of cell functions such as proliferation and differentiation, can be characteristically modulated in cells migrating on a matrix with stiffness-heterogeneity, it has been unclear how the mode of fluctuation of ISD affects cell functions. In the present study, we demonstrate that mesenchymal stem cells (MSCs) dual-durotaxing (i.e., both forward and reverse durotaxis) on microelastically-patterned gels with stiff triangular domains markedly amplify the fluctuation of ISD, nuclear shape, and the spatial distribution of chromatins, which makes the cells remain far from tensional equilibrium. We provide evidence that amplified chromatin fluctuation in the dual-durotaxing MSCs can cause activation of cellular vigor and maintenance of the stemness.

biophysics↗

Epidemiological survey of serum titers from adults against various Gram-negative bacterial V-antigens

The V-antigen, a virulence-associated protein, was first identified in Yersinia pestis more than half a century ago. Since then, other V-antigen homologs and orthologs have been discovered and are now considered vital molecules for the toxic effects mediated by the type III secretion system in infections caused by various pathogenic Gram-negative bacteria. After purifying recombinant V-antigen proteins including PcrV from Pseudomonas aeruginosa, LcrV from Yersinia, LssV from Photorhabdus luminescens, AcrV from Aeromonas salmonicida, and VcrV from Vibrio parahaemolyticus, we developed an enzyme-linked immunoabsorbent assay to measure titers against each V-antigen in the sera collected from 186 adult volunteers. Different titer-specific correlation levels were determined for the five V-antigens. The anti-LcrV and anti-AcrV titers shared the highest correlation with each other, with a correlation coefficient of 0.84. The next highest correlation coefficient was between anti-AcrV and anti-VcrV titers at 0.79, while the lowest correlation was found between anti-LcrV and anti-VcrV titers, which were still higher than 0.7 Sera from mice immunized with one of the five recombinant V-antigens displayed cross-antigenicity with some of the other four V-antigens, supporting the results from the human sera. Thus, the serum anti-V-antigen titer measurement system could potentially be used for epidemiological investigations on various pathogenic Gram-negative bacteria.

immunology↗