Biomimetic Strategies for the Glioblastoma Microenvironment

Glioblastoma multiforme (GBM) is a devastating type of tumor with high mortality, caused by extensive infiltration into adjacent tissue and rapid recurrence. Most therapies for GBM have focused on the cytotoxicity and have not targeted GBM spread. However, there have been numerous attempts to improve therapy by addressing GBM invasion, through understanding and mimicking its behavior using three-dimensional (3D) experimental models. Compared with two-dimensional models and in vivo animal models, 3D GBM models can capture the invasive motility of glioma cells within a 3D environment comprising many cellular and non-cellular components. Based on tissue engineering techniques, GBM invasion has been investigated within a biologically relevant environment, from biophysical and biochemical perspectives, to clarify the pro-invasive factors of GBM. This review discusses the recent progress in techniques for modeling the microenvironments of GBM tissue and suggests future directions with respect to recreating the GBM microenvironment and preclinical applications

Crack/Fold Hybrid Structure-Based Fluidic Networks Inspired by the Epidermis of Desert Lizards

A bioinspired fluidic system with cracks and folds was introduced to emulate the structures and functions of desert lizards’ integuments, which show marked ability of water management. Because there was a structural analogy between scales and interscalar channels of lizard’s skin and cracks and folds of a bilayer elastic material, we can mimic lizard’s skin by controlling the stress distribution on patterned elastomers. Our system showed not only capillary-driven water retention within confined fluidic network, but also stretching-driven biaxial water transport. Observed features of our system may enhance understanding of water management in relation to morphogenetic aspects of lizards

Nanoengineered, cell-derived extracellular matrix influences ECM-related gene expression of mesenchymal stem cells

Abstract Background Human mesenchymal stem cells (hMSCs) are, due to their pluripotency, useful sources of cells for stem cell therapy and tissue regeneration. The phenotypes of hMSCs are strongly influenced by their microenvironment, in particular the extracellular matrix (ECM), the composition and structure of which are important in regulating stem cell fate. In reciprocal manner, the properties of ECM are remodeled by the hMSCs, but the mechanism involved in ECM remodeling by hMSCs under topographical stimulus is unclear. In this study, we therefore examined the effect of nanotopography on the expression of ECM proteins by hMSCs by analyzing the quantity and structure of the ECM on a nanogrooved surface. Methods To develop the nanoengineered, hMSC-derived ECM, we fabricated the nanogrooves on a coverglass using a UV-curable polyurethane acrylate (PUA). Then, hMSCs were cultivated on the nanogrooves, and the cells at the full confluency were decellularized. To analyze the effect of nanotopography on the hMSCs, the hMSCs were re-seeded on the nanoengineered, hMSC-derived ECM. Results hMSCs cultured within the nano-engineered hMSC-derived ECM sheet showed a different pattern of expression of ECM proteins from those cultured on ECM-free, nanogrooved surface. Moreover, hMSCs on the nano-engineered ECM sheet had a shorter vinculin length and were less well-aligned than those on the other surface. In addition, the expression pattern of ECM-related genes by hMSCs on the nanoengineered ECM sheet was altered. Interestingly, the expression of genes for osteogenesis-related ECM proteins was downregulated, while that of genes for chondrogenesis-related ECM proteins was upregulated, on the nanoengineered ECM sheet. Conclusions The nanoengineered ECM influenced the phenotypic features of hMSCs, and that hMSCs can remodel their ECM microenvironment in the presence of a nanostructured ECM to guide differentiation into a specific lineage

The complete mitochondrial genome information of Phoxinus phoxinus (Cypriniformes: Cyprinidae) on the Korean Peninsula and the phylogenetic implication

Phoxinus phoxinus is a small Leuciscinae species predominantly found in cool and well-oxygenated streams throughout a wide area encompassing Europe, Siberia and East Asia. It is believed that the populations in Korea hold important clues to how the species has been distributed south along the Eurasian continent to the Korean Peninsula. We characterized the complete mitochondrial genomes of two individual fin-clip samples collected from the two Korean river systems. The whole sequences were 17,665 and 18,220 bp, respectively, and included 13 protein-coding genes, 2 ribosomal RNA genes and 22 transfer RNA genes. The genome size difference was due to the considerably different sizes of the control region. The overall genome structures were identical to those observed in other Leuciscinae species

Nanovilli based reverse uptake plarform for highly efficient intracellular delivery and transfection

Intracellular delivery of macromolecules is a significant technique in research and therapeutic applications. However, conventional vector-based and physical methods, which rely on exogenous material, high energy particle, or electrical field, can cause toxicity or off-target effects. To overcome this issue, we have targeted mechanical deformation of cellular membrane, which can lead to higher cellular uptake rate. Here, we demonstrated nano-villi platform that can mechanically stimulate cells and enhance intracellular delivery rate. By testing transfection efficiency with GFP expressing HeLa cells, it was found out that the transfection efficiency was significantly increased when nano-scale structures existed on the surface

Assessing Spatial Distribution of Multicellular Self-Assembly Enables the Prediction of Phenotypic Heterogeneity in Glioblastoma

Phenotypic heterogeneity of glioblastomas is a leading determinant of therapeutic resistance and treatment failure. However, functional assessment of the heterogeneity of glioblastomas is lacking. We developed a self-assembly-based assessment system that predicts inter/intracellular heterogeneity and phenotype associations, such as cell proliferation, invasiveness, drug responses, and gene expression profiles. Under physical constraints for cellular interactions, mixed populations of glioblastoma cells are sorted to form a segregated architecture, depending on their preference for binding to cells of the same phenotype. Cells distributed at the periphery exhibit a reduced temozolomide (TMZ) response and are associated with poor patient survival, whereas cells in the core of the aggregates exhibit a significant response to TMZ. Our results suggest that the multicellular self-assembly pattern is indicative of the intertumoral and intra-patient heterogeneity of glioblastomas, and is predictive of the therapeutic response

Complete mitochondrial genome of two shorebirds (Charadriiformes: Scolopacidae), great knot (Calidris tenuirostris) and bar-tailed godwit (Limosa lapponica)

The mitochondrial genome of Calidris tenuirostris and Limosa lapponica were described using the whole mitochondrial genome obtained from Illumina Next-Generation Sequencing (NGS) technology. Total length of the mitogenome of C. tenuirostris was 16,732bp with slight A+T bias (55.3%). Genome size of L. lapponica was 16,773bp long and A+T biased (56.3%). Both gemones consisting of 2 rRNAs, 13 protein-coding genes, 22 tRNA genes and 1 non-coding regions. This is the first report of complete mitogenomes of these two shorebird species, (C. tenuirostris and of L. lapponica). We observed paraphyletic relationship among the species in the Family Scolopacidae. Also our result showed analogous patterns with the previous studies on the parallel relationships of shorebird species. This study provides basic genetic information for help in understanding phylogenetic relationships . within the Charadriiformes

Assessing Spatial Distribution of Multicellular Self-Assembly Enables the Prediction of Phenotypic Heterogeneity in Glioblastoma

Phenotypic heterogeneity of glioblastomas is a leading determinant of therapeutic resistance and treatment failure. However, functional assessment of the heterogeneity of glioblastomas is lacking. We developed a self-assembly-based assessment system that predicts inter/intracellular heterogeneity and phenotype associations, such as cell proliferation, invasiveness, drug responses, and gene expression profiles. Under physical constraints for cellular interactions, mixed populations of glioblastoma cells are sorted to form a segregated architecture, depending on their preference for binding to cells of the same phenotype. Cells distributed at the periphery exhibit a reduced temozolomide (TMZ) response and are associated with poor patient survival, whereas cells in the core of the aggregates exhibit a significant response to TMZ. Our results suggest that the multicellular self-assembly pattern is indicative of the intertumoral and intra-patient heterogeneity of glioblastomas, and is predictive of the therapeutic response