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Bioprinting of 3D convoluted renal proximal tubules on perfusable chips

Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen. These engineered 3D proximal tubules on chip exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D controls with or without perfusion. Upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. Our bioprinting method provides a new route for programmably fabricating advanced human kidney tissue models on demand.

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Colorectal adenocarcinoma stem cells show distinct growth patterns depending on the culture environment

"Disease models for basic cancer research rely predominantly on established cell lines and animal studies. Lgr5, an R-spondin receptor, and a specific marker of gastrointestinal tract stem cells, enabled in vitro culture and observation of all steps of their differentiation and self-organization from single cells to “mini-organs”. Organoid cultures are currently the state-of-theart model for studies of colon, esophagus and small intestine pathophysiology. We used this method to produce cancer colonoids from stem cells, isolated from LoVo cell line. LoVo cell line, established from Dukes’ type C, grade IV, colorectal adenocarcinoma, contains, according to the literature, a significant fraction of cancer stem cells (CSCs). CSCs derived from LoVo cell line present distinct growth patterns with varying culture, environment. In 2D, they form a monolayer of spindleshaped cells, in 3D they generate round, spherical structures with smooth edges. As organoids should develop all cell types, present in vivo in human colon, we plan to investigate cell subtypes present in LoVo ‘colonoids’. Also, patterns of demethylation induced changes in gene expression are under evaluation by microarrays."

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Insights into the role of sulfated glycans in cancer cell adhesion and migration through use of branched peptide probe

The tetra-branched peptide NT4 selectively binds to different human cancer cells and tissues. NT4 specifically binds to sulfated glycosaminoglycans on cancer cell membranes. Since sulfated glycosaminoglycans are involved in cancer cell interaction with the extracellular matrix, we evaluated the effect of NT4 on cancer cell adhesion and migration. We demonstrated here that the branched peptide NT4 binds sulfated glycosaminoglycans with high affinity and with preferential binding to heparan sulfate. NT4 inhibits cancer cell adhesion and migration on different proteins, without modifying cancer cell morphology or their ability to produce protrusions, but dramatically affecting the directionality and polarity of cell movement. Results obtained by taking advantage of the selective targeting of glycosaminoglycans chains by NT4, provide insights into the role of heparan sulfate proteoglycans in cancer cell adhesion and migration and suggest a determinant role of sulfated glycosaminoglycans in the control of cancer cell directional migration.

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Comparison of Normal and Asthmatic Bronchial Epithelial Cells and Smooth Muscle Cells in Monolayer and RAFT™ 3D Cell Culture System

Remodeling of the lung is considered as a feature of asthma. To better understand the differences between normal and diseased lung cells, we studied Clonetics™ human Bronchial Epithelial Cells from normal and asthmatic donors (NHBE and DHBE-AS, respectively), and human Bronchial Smooth Muscle Cells (BSMC and DBSMC, respectively) donors in two-dimensional (2D) culturing surfaces and a three-dimensional (3D) cell culture system. Three-dimensional cell culture systems aim to provide cells with a more natural growth environment with the help of methods such as hydrogel matrices or synthetic scaffolds. The environmental cues cells experience in a 3D cell culture environment bring them closer to their in-vivo state with respect to cellular structure, interaction with neighboring cells and overall cell functionality as compared to traditional flat two-dimensional (2D) culturing surfaces. Collagen, in particular collagen type I, is one of the most abundant extracellular matrix proteins in the body, and therefore an often-used 3D cell culture material for several cell types. Lonza offers the novel RAFT™ (Real Architecture for 3D Tissue) 3D cell culture system that allows the creation of tissue-like structures with cells growing within or on top of a compressed, high-density collagen scaffold. This novel tool allowed us to gain understanding of the differences between normal and asthmatic cells in single- and co-culture of bronchial epithelial cells with their corresponding smooth muscle counterparts. Real time imaging of 2D cultures were obtained by using the new CytoSMART™ Lux 10X System. The characteristics and functional changes of cells from normal and asthmatic human donor lung tissues were assayed in both 2D and RAFT™ 3D cell cultures. Proliferation was performed with the ViaLight™ Plus assay, which measures total ATP. Immunofluorescence imaging allowed confirmation of cell identity and morphology. Metabolite evaluation was carried out to assess culture characteristics. ELISA analysis was carried out to evaluate the secretions of chemokines, cytokines and growth factors.

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Oncoimmunology, a practical guide for cancer immunotherapy

In this book, leading experts in cancer immunotherapy join forces to provide a comprehensive guide that sets out the main principles of oncoimmunology and examines the latest advances and their implications for clinical practice, focusing in particular on drugs with FDA/EMA approvals and breakthrough status. The aim is to deliver a landmark educational tool that will serve as the definitive reference for MD and PhD students while also meeting the needs of established researchers and healthcare professionals.

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Investigation of osseointegration of three 3D printed titanium scaffold structures

In this study, the amount of osteoblastic growth on three different scaffolds was compared. Three different scaffolds were designed to have seventy-five percent porosity as a constant and the repeated unit cell size and wall thickness were varied. The first scaffold had a unit cell size of 0.3 millimeters and the thinnest wall, the second had a 0.4-millimeter unit cell size and the middle wall thickness, the last had a 0.5-millimeter unit cell size and the thickest walls. The wall thickness was adjusted to ensure the consistent seventy-five percent porosity. Five scaffolds of each design were printed of titanium by Tangible Solutions, cleaned via sonication in distilled water, and autoclaved for sterility. Each scaffold was then placed in its own 3.9 cm^2 well and seeded with four thousand cells per square centimeter. Scaffolds were kept in culture for four days in standard conditions, with media changed every other day. On the fourth day, scaffolds were immersed in trypsin and rocked to ensure detachment of all cells. Counts were then taken using the CytoSMART automated hemocytometer and groups were compared. Results indicate significant cell growth and proliferation on all three scaffold designs after four days of culture. Average cell counts per scaffold were 36700 cells (±6817 cells) for the 3 unit cell scaffolds, 29810 cells (±8824 cells) for the 4 unit cell scaffolds, and 31435 cells (±cells) for the 5 unit cell scaffolds. Statistical analysis using JMP was performed, and no significant difference was found between groups. However, this study had a fairly small sample size (n=5). Plans are underway to repeat the experiment in order to obtain more data points per group.

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Establishment of a three-dimensional Tumor Culture Model

The development of 3D cell culture techniques has begun to offer promising results for the field of cancer biology research in recent years, however, it is necessary to continue experimenting with protocols for tumor cells and to analyze their advantages or shortcomings with new Cell lines and / or material extracted from biopsies of different types of tumors for which culturing techniques of any kind have not yet been standardized. Therefore, this work aimed to establish a three-dimensional tumor culture model using the multicellular tumor spheroids (MTS) technique from tumor cell lines and biopsies of gastric and endometrial cancer tumors, establishing protocols For their sowing and analysis. The spheroids were cultured from the SiHa cell line, starting from monolayer cultures that were subsequently trypsinized to establish an ideal concentration that was seeded in wells coated with 1% agarose. With the spheroids already formed, tests are being carried out to make cuts that allow to observe the internal structure of the same, which are still in the analysis phase. At the end of the working time, it was possible to establish the protocol for the sowing of a three-dimensional cell culture using the multicellular tumor spheroid technique (MTS) from the SiHa cell line, as well as to seed these spheroids from the cultures Established primary tumor cells of gastric and endometrial cancer. This protocol opens the door to new research on gene silencing and virus penetration in more complex tumor systems.

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