Kidney organoids derived from human pluripotent stem cells exhibit glomerular- and tubular-like compartments that are largely avascular and immature in static culture. Here, we report an in vitro method for culturing kidney organoids under flow on millifluidic chips, which greatly expands their endogenous pool of endothelial progenitor cells (EPCs) and generates vascular networks with perfusable lumens surrounded by mural cells. Vascularized kidney organoids cultured under flow exhibit more mature podocyte and tubular compartments with enhanced cellular polarity and adult gene expression, compared to static controls. However, the association of vessels with these compartments is reduced upon disrupting the endogenous VEGF gradient. Glomerular vascular development progresses through intermediate stages akin to the embryonic mammalian kidney’s formation of capillary loops abutting foot processes. The ability to induce substantial vascularization and morphological maturation of kidney organoids in vitro under flow opens new avenues for studying kidney development, disease, and regeneration.
Much of the information on the Cytochrome P450 enzymes (CYPs) is spread across literature and the internet. Aggregating knowledge about CYPs into one database makes the search more efficient. Text mining on 57 CYPs and drugs led to a mass of papers, which were screened manually for facts about metabolism, SNPs and their effects on drug degradation. Information was put into a database, which enables the user not only to look up a particular CYP and all metabolized drugs, but also to check tolerability of drug-cocktails and to find alternative combinations, to use metabolic pathways more efficiently. The SuperCYP database contains 1170 drugs with more than 3800 interactions including references. Approximately 2000 SNPs and mutations are listed and ordered according to their effect on expression and/or activity. SuperCYP (http://bioinformatics.charite.de/supercyp) is a comprehensive resource focused on CYPs and drug metabolism. Homology-modeled structures of the CYPs can be downloaded in PDB format and related drugs are available as MOL-files. Within the resource, CYPs can be aligned with each other, drug-cocktails can be ‘mixed’, SNPs, protein point mutations, and their effects can be viewed and corresponding PubMed IDs are given. SuperCYP is meant to be a platform and a starting point for scientists and health professionals for furthering their research.
Acoustophoretic printing enables patterning of complex fluids ranging from cell-laden hydrogels to liquid metals.
To date, several methods have been developed to induce alignment in engineered cardiac tissues. [7][8][9][10][11] One common approach is to seed cardiomyocytes onto micro-or nanopatterned surfaces that contain topographical cues, which guide cellular alignment. [12,13] Another approach is to seed cells onto anisotropic polymer scaffolds [14][15][16] or decellularized matrices [17] that guide tissue alignment. In addition, cell-laden hydrogels seeded into molds of varying geometry can self-assemble into aligned cardiac rods, rings, bundles, and sheets. [18][19][20][21][22][23][24] Unfortunately, these methods are typically confined to thin cardiac tissues (≤100 µm thick) with either linear or radial alignment. By contrast, extrusionbased bioprinting offers broad flexibility to control tissue composition and architecture. Recently, we and others have demonstrated that synthetic and biological fibers exhibit shear-induced alignment during printing, opening the possibility to program tissue alignment via cell templating. [25][26][27][28][29][30][31][32][33][34] However, programming the architecture of human tissues by directly aligning anisotropic tissue building blocks has yet to be explored.Here, we report the fabrication of engineered cardiac tissue with programmable alignment via bioprinting of anisotropic organ building blocks (aOBBs) (Figure 1). These aOBBs are elongated microtissues composed of cellular aligned hiPSC-CMs that can be modularly assembled into a printable bioink (Figure 1a). Individual aOBBs within this bioink align along the print path due to the same shear and extensional forces that orient acellular fibers upon extrusion through a tapered nozzle (Figure 1b). [35] Using this method, we fabricated cardiac tissues with high cellular density and programmed alignment across multiple length scales; ranging from individual aOBBs to the sarcomeric machinery that drives their contractile function (Figure 1c). Results and DiscussionThe first step in creating our cardiac bioink is to fabricate scalable micropillar arrays by stereolithography (SLA). These micropillar arrays are used to generate tens of thousands of aOBBs with controlled aspect ratio and cellular composition. After optimizing these parameters, we employed a sequential transfer micromolding process to create a single contiguousThe ability to replicate the 3D myocardial architecture found in human hearts is a grand challenge. Here, the fabrication of aligned cardiac tissues via bioprinting anisotropic organ building blocks (aOBBs) composed of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) is reported. A bioink composed of contractile cardiac aOBBs is first generated and aligned cardiac tissue sheets with linear, spiral, and chevron features are printed. Next, aligned cardiac macrofilaments are printed, whose contractile force and conduction velocity increase over time and exceed the performance of spheroid-based cardiac tissues. Finally, the ability to spatially control the magnitude and direction of contractile force...
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