Additional file 1 of Phenotypic change of mesenchymal stem cells into smooth muscle cells regulated by dynamic cell-surface interactions on patterned arrays of ultrathin graphene oxide substrates

Additional file 1: Figure S1. Raman spectra on rGO and glass area. Figure S2. Optical transmittance of gradient rGO stripe pattern and rGO film. Figure S3. XPS spectra of C1s (a) and N1s (b) of the APTES-modified glass substrate. Figure S4. (a) Optical micrographs of MSCs on glass and rGO surface (b) Proliferation of MSCs on the tissue culture plate, glass, and rGO substrate. Figure S5. The magnified single-line pattern of MSCs depending on rGO/glass pattern spacing. Figure S6. Time-lapse image in recording MSCs movement on the 100 μm pattern spacing of glass/rGO. Figure S7. AFM image and height profiles of the micropatterned glass/rGO substrate. Figure S8. Potential distribution mapping for the surface charge at the glass/rGO region. Figure S9. Cell-to-Cell interaction between the aligned MSCs on glass/rGO patterned substrate. Figure S10. MSCs behavior on the unpatterned glass substrate. Figure S11. Real-time observations for the migration of MSCs cultured on 40 μm pattern spacing of glass/rGO. Figure S12. Histogram of the angular orientation of MSCs distributed by the glass/rGO pattern spacing formed on the cell substrate. Figure S13. Captured micrographs from time-lapse observations in recording MSCs migration on the cross-patterned glass surrounded by rGO. Figure S14. Cytoskeletal arrangement of MSCs cultured on the cross-patterned glass surrounded by rGO. Figure S15. The culture protocol to induce the quiescence of MSCs and TGF-β1-induced differentiation into SMCs. Figure S16. Quiescent MSCs cultured on 40 μm pattern spacing of rGO/glass. Figure S17. Angular orientation of quiescent MSCs distributed by the glass/rGO pattern spacing. Figure S18. TGF-β1-induced differentiation of MSCs to SMCs on the gradient patterned rGO/glass substrate. Figure S19. Flow cytometry analysis of SMC-specific markers for quiescent MSCs cultured on the pattern spacing of 100 μm; the peaks demonstrate direct comparison to TGF-β1-induced SMCs. Figure S20. (a) Representative optical micrographs of contractile collagen gel. (b) The measured result on the reduction of collagen gel surface area; the data shown as the mean ± SD (n=3). *P<0.05 Figure S21. YAP/TAZ expression of quiescent MSCs cultured on an anisotropic rGO/glass patterned substrate. Table S1. List of antibodies used in the present study. WB: western blotting/ICC: immunocytochemistry. Table S2. Peak area ratios of the oxygen-containing group to the C-C bond obtained by XPS

Proteomic Analysis of Tumor Necrosis Factor-α-Induced Secretome of Human Adipose Tissue-Derived Mesenchymal Stem Cells

Human adipose tissue-derived mesenchymal stem cells (hASCs) are useful for regeneration of inflamed or injured tissues. To identify secreted hASC proteins during inflammation, hASCs were exposed to tumor necrosis factor-α (TNF-α) and conditioned media derived from hASCs were analyzed by liquid chromatography coupled with tandem mass spectrometry. We identified 187 individual proteins as secreted proteins (secretome) in hASC-conditioned media; 118 proteins were secreted at higher levels upon TNF-α treatment. The TNF-α-induced secretome included a variety of cytokines and chemokines such as interleukin-6 (IL-6), IL-8, chemokine (C-X-C motif) ligand 6, and monocyte chemotactic protein-1 (MCP-1). TNF-α also increased expression of various proteases including cathepsin L, matrix metalloproteases and protease inhibitors, and induced secretion of long pentraxin 3, a key inflammatory mediator implicated in innate immunity. TNF-α-conditioned media stimulated migration of human monocytes, which play a key role in inflammatory responses. This migration was abrogated by pretreatment with neutralizing anti-IL-6, anti-IL-8, and anti-MCP-1 antibodies, suggesting that IL-6, IL-8, and MCP-1 are involved in migration of monocytes. Taken together, these results suggest that TNF-α-induced secretome may play a pivotal role in inflammatory responses and that shotgun proteomic analysis will be useful for elucidation of the paracrine functions of mesenchymal stem cells

Selective Interbundle Cross-Linking for Lightweight and Superstrong Carbon Nanotube Yarns

In this study, a range of carbon nanotube yarn (CNTY) architectures was examined and controlled by chemical modification to gain a deeper understanding of CNTY load-bearing systems and produce lightweight and superstrong CNTYs. The architecture of CNTY, which has polymer layers surrounding a compact bundle without hampering the original state of the CNTs in the bundle, is a favorable design for further chemical cross-linking and for enhancing the load-transfer efficiency, as confirmed by in situ Raman spectroscopy under a stress load. The resulting CNTY exhibited excellent mechanical performance that exceeded the specific strength of the benchmark, high-performance fibers. This exceptional strength of the CNTY makes it a promising candidate for the cable of a space elevator traveling from the Earth to the International Space Station given its strength of 4.35 GPa/(g cm–3), which can withstand the self-weight of a 440 km cable

Revisiting the Role of Graphene Quantum Dots in Ternary Organic Solar Cells: Insights into the Nanostructure Reconstruction and Effective Förster Resonance Energy Transfer

Recent studies have introduced the graphene quantum dot (GQD) as a third material for the bulk-heterojunction polymer:fullerene solar cell (PSC) to improve light conversion efficiency. Although exciton generation/dissociation and carrier transport in the GQD-incorporated light-absorbing layer are strongly influenced by the ternary component, detailed analysis on the role of GQD in the light-absorbing layer is lacking. In this study, a perspective on origin of improved photovoltaic performance of GQD-incorporated PSC is provided. The Förster resonance energy transfer (FRET) from GQD to polymer:fullerene and reorganization of the ternary-component film are analyzed. The GQD chemical nature difference after controlling nitrogen functionality affects the quantum yield (QY) and surface energy. Because the GQD is distributed in the fullerene-rich domain, actual improvements in the FRET to polymer-rich phase are not great, despite the improved QY and red-shifted photoluminescence. However, changes in the surface energy affect the degree of crystallinity of polymer domains and nanophase separation in polymer:fullerene films. The intense FRET from GQD to fullerene and favorable changes in the nanostructure lead to the enhancing the power conversion efficiency of GQD-containing ternary PSC

Yolk–Shell-Type Gold Nanoaggregates for Chemo- and Photothermal Combination Therapy for Drug-Resistant Cancers

Epithelial ovarian cancer is a gynecological cancer with the highest mortality rate, and it exhibits resistance to conventional drugs. Gold nanospheres have gained increasing attention over the years as photothermal therapeutic nanoparticles, owing to their excellent biocompatibility, chemical stability, and ease of synthesis; however, their practical application has been hampered by their low colloidal stability and photothermal effects. In the present study, we developed a yolk–shell-structured silica nanocapsule encapsulating aggregated gold nanospheres (aAuYSs) and examined the photothermal effects of aAuYSs on cell death in drug-resistant ovarian cancers both in vitro and in vivo. The aAuYSs were synthesized using stepwise silica seed synthesis, surface amino functionalization, gold nanosphere decoration, mesoporous organosilica coating, and selective etching of the silica template. Gold nanospheres were agglomerated in the confined silica interior of aAuYSs, resulting in the red-shifting of absorbance and enhancement of the photothermal effect under 808 nm laser irradiation. The efficiency of photothermal therapy was first evaluated by inducing aAuYS-mediated cell death in A2780 ovarian cancer cells, which were cultured in a two-dimensional culture and a three-dimensional spheroid culture. We observed that photothermal therapy using aAuYSs together with doxorubicin treatment synergistically induced the cell death of doxorubicin-resistant A2780 cancer cells in vitro. Furthermore, this type of combinatorial treatment with photothermal therapy and doxorubicin synergistically inhibited the in vivo tumor growth of doxorubicin-resistant A2780 cancer cells in a xenograft transplantation model. These results suggest that photothermal therapy using aAuYSs is highly effective in the treatment of drug-resistant cancers

Yolk–Shell-Type Gold Nanoaggregates for Chemo- and Photothermal Combination Therapy for Drug-Resistant Cancers

Epithelial ovarian cancer is a gynecological cancer with the highest mortality rate, and it exhibits resistance to conventional drugs. Gold nanospheres have gained increasing attention over the years as photothermal therapeutic nanoparticles, owing to their excellent biocompatibility, chemical stability, and ease of synthesis; however, their practical application has been hampered by their low colloidal stability and photothermal effects. In the present study, we developed a yolk–shell-structured silica nanocapsule encapsulating aggregated gold nanospheres (aAuYSs) and examined the photothermal effects of aAuYSs on cell death in drug-resistant ovarian cancers both in vitro and in vivo. The aAuYSs were synthesized using stepwise silica seed synthesis, surface amino functionalization, gold nanosphere decoration, mesoporous organosilica coating, and selective etching of the silica template. Gold nanospheres were agglomerated in the confined silica interior of aAuYSs, resulting in the red-shifting of absorbance and enhancement of the photothermal effect under 808 nm laser irradiation. The efficiency of photothermal therapy was first evaluated by inducing aAuYS-mediated cell death in A2780 ovarian cancer cells, which were cultured in a two-dimensional culture and a three-dimensional spheroid culture. We observed that photothermal therapy using aAuYSs together with doxorubicin treatment synergistically induced the cell death of doxorubicin-resistant A2780 cancer cells in vitro. Furthermore, this type of combinatorial treatment with photothermal therapy and doxorubicin synergistically inhibited the in vivo tumor growth of doxorubicin-resistant A2780 cancer cells in a xenograft transplantation model. These results suggest that photothermal therapy using aAuYSs is highly effective in the treatment of drug-resistant cancers

Phospholipid End-Capped Bioreducible Polyurea Micelles as a Potential Platform for Intracellular Drug Delivery of Doxorubicin in Tumor Cells

Bioreducible polymeric nanocarriers bearing disulfide bonds have been widely used for intracellular therapeutic delivery, since they are quickly sliced or reduced in the reductive milieu of cytosol. Incorporation of hydrophobic phospholipid analogues to polymers improves the biocompatibility by reducing the protein adsorption and platelet adhesion on the cell membranes. In this study, we have developed a series of bioreducible polyureas (PUs) bearing disulfide linkages in their backbone and phospholipid moieties in their chain ends. The reducible PUs exhibit interesting self-assembly behavior and controlled release profiles at intracellular mimic conditions. The self-assembled hybrid nanocarriers with an average diameter of about 110 nm efficiently encapsulated the model anticancer drug doxorubicin (Dox). The <i>in vitro</i> Dox release profile demonstrated a good glutathione (GSH)-responsive release of Dox at 10 mM GSH. An <i>in vitro</i> cell viability assay was also performed with various cell lines. The antitumor activity tests using HCT15 and HCT116 cancer cells showed that Dox-loaded nanocarriers bearing disulfide linkages induced significantly higher cytotoxicity in cancer cells than those without disulfide linkages. Hence, the PU nanocarriers bearing disulfide linkers and α,ω-phospholipid moieties have a promising potential to trigger the drug into the intracellular compartment of cancer cells

Periostin Accelerates Bone Healing Mediated by Human Mesenchymal Stem Cell-Embedded Hydroxyapatite/Tricalcium Phosphate Scaffold

<div><p>Background</p><p>Periostin, an extracellular matrix protein, is expressed in bone, more specifically, the periosteum and periodontal ligaments, and plays a key role in formation and metabolism of bone tissues. Human adipose tissue-derived mesenchymal stem cells (hASCs) have been reported to differentiate into osteoblasts and stimulate bone repair. However, the role of periostin in hASC-mediated bone healing has not been clarified. In the current study, we examined the effect of periostin on bone healing capacity of hASCs in a critical size calvarial defect model.</p><p>Methods and Results</p><p>Recombinant periostin protein stimulated migration, adhesion, and proliferation of hASCs <i>in vitro</i>. Implantation of either hASCs or periostin resulted in slight, but not significant, stimulation of bone healing, whereas co-implantation of hASCs together with periostin further potentiated bone healing. In addition, the number of Ki67-positive proliferating cells was significantly increased in calvarial defects by co-implantation of both hASCs and periostin. Consistently, proliferation of administered hASCs was stimulated by co-implantation with periostin <i>in vivo</i>. In addition, co-delivery of hASCs with periostin resulted in markedly increased numbers of CD31-positive endothelial cells and α-SMA-positive arterioles in calvarial defects.</p><p>Conclusions</p><p>These results suggest that recombinant periostin potentiates hASC-mediated bone healing by stimulating proliferation of transplanted hASCs and angiogenesis in calvarial defects.</p></div