Explore the vast range of titles available.

Bioprinting promises enormous control over the spatial deposition of cells in three dimensions 1 – 7 , but current approaches have had limited success at reproducing the intricate micro-architecture, cell-type diversity and function of native tissues formed through cellular self-organization. We introduce a three-dimensional bioprinting concept that uses organoid-forming stem cells as building blocks that can be deposited directly into extracellular matrices conducive to spontaneous self-organization. By controlling the geometry and cellular density, we generated centimetre-scale tissues that comprise self-organized features such as lumens, branched vasculature and tubular intestinal epithelia with in vivo-like crypts and villus domains. Supporting cells were deposited to modulate morphogenesis in space and time, and different epithelial cells were printed sequentially to mimic the organ boundaries present in the gastrointestinal tract. We thus show how biofabrication and organoid technology can be merged to control tissue self-organization from millimetre to centimetre scales, opening new avenues for drug discovery, diagnostics and regenerative medicine. A 3D bioprinting approach has been developed to facilitate tissue morphogenesis by directly depositing organoid-forming stem cells in an extracellular matrix, with the ability to generate intestinal epithelia and branched vascular tissue constructs.

Eukaryotic cells rely on long-lived microtubules for intracellular transport and as compression-bearing elements. We considered that long-lived microtubules are acetylated inside their lumen and that microtubule acetylation may modify microtubule mechanics. Here, we found that tubulin acetylation is required for the mechanical stabilization of long-lived microtubules in cells. Depletion of the tubulin acetyltransferase TAT1 led to a significant increase in the frequency of microtubule breakage. Nocodazole-resistant microtubules lost upon removal of acetylation were largely restored by either pharmacological or physical removal of compressive forces. In in vitro reconstitution experiments, acetylation was sufficient to protect microtubules from mechanical breakage. Thus, acetylation increases mechanical resilience to ensure the persistence of long-lived microtubules.

During mouse pre-implantation development, the formation of the blastocoel, a fluid-filled lumen, breaks the radial symmetry of the blastocyst. The factors that control the formation and positioning of this basolateral lumen remain obscure. We found that accumulation of pressurized fluid fractures cell-cell contacts into hundreds of micrometer-size lumens. These microlumens eventually discharge their volumes into a single dominant lumen, which we model as a process akin to Ostwald ripening, underlying the coarsening of foams. Using chimeric mutant embryos, we tuned the hydraulic fracturing of cell-cell contacts and steered the coarsening of microlumens, allowing us to successfully manipulate the final position of the lumen.We conclude that hydraulic fracturing of cell-cell contacts followed by contractility-directed coarsening of microlumens sets the first axis of symmetry of the mouse embryo.

To evaluate the efficacy of endovascular circulating false lumen occlusion (CFLO) in inducing positive aortic remodeling in chronic aneurysmal descending aortic dissection (AD). This retrospective monocentric study included patients treated by CFLO between 2003 and 2022 in the context of chronic AD with progressive descending aneurysmal evolution and persistent circulating false lumen (FL). The procedure was achieved with coils, plugs, and/or glue at the entry tear or in the FL and/or with covered stenting in the supra-aortic trunk. The primary endpoint evaluated the positive aortic remodeling, defined as stabilization or a decrease in the aortic diameter on a computed tomography scan at the 1-year follow-up after the procedure. The FL circulating status, safety, and occurrence of aneurysm events during follow-up were also evaluated. Twenty patients [median age: 65.4 years, interquartile range (IQR): 58.4–69.9; 13 men] were included, with a median duration from an acute AD of 32.5 months (IQR: 8.8–76.5). Twelve patients (60%) achieved complete FL thrombosis after CFLO, whereas 8/20 patients (40.0%) experienced partial thrombosis. Additionally, positive aortic remodeling was observed in 13 patients (65%). Following the procedure, the aneurysmal aortic diameter decreased in 8/20 patients (40.0%) and remained stable in 5/20 patients (25.0%). Two patients (10%) had complications related to the procedure. Two patients (10%) had secondary aneurysm events during follow-up. CFLO is a feasible and efficient method to induce FL thrombosis and reduce aneurysmal progression in chronic AD. The positive outcomes observed highlight the potential of this technique to improve patient management in complex aortic pathologies. This approach offers a valuable option in the management of chronic AD and emphasizes the importance of endovascular interventions in enhancing patient outcomes.

Kidney organoids derived from human pluripotent stem cells have 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 expands their endogenous pool of endothelial progenitor cells and generates vascular networks with perfusable lumens surrounded by mural cells. We found that vascularized kidney organoids cultured under flow had more mature podocyte and tubular compartments with enhanced cellular polarity and adult gene expression compared with that in static controls. Glomerular vascular development progressed through intermediate stages akin to those involved in the embryonic mammalian kidney’s formation of capillary loops abutting foot processes. The association of vessels with these compartments was reduced after disruption of the endogenous VEGF gradient. The ability to induce substantial vascularization and morphological maturation of kidney organoids in vitro under flow opens new avenues for studies of kidney development, disease, and regeneration.Culturing human kidney organoids under fluidic shear conditions leads to robust vascularization and increased maturity. These kidney organoids should serve as a better model for kidney development than those developed in static culture.

The endothelial cell (EC) outgrowth in both vasculogenesis and angiogenesis starts with remodeling surrounding matrix and proceeds with the crosstalk between cells for the multicellular vasculature formation. The mechanical plasticity of matrix, defined as the ability to permanently deform by external traction, is pivotal in modulating cell behaviors. Nevertheless, the implications of matrix plasticity on cell-to-cell interactions during EC outgrowth, along with the molecular pathways involved, remain elusive. Here we develop a collagen-hyaluronic acid based hydrogel platform with tunable plasticity by using compositing strategy of dynamic and covalent networks. We show that although the increasing plasticity of the hydrogel facilitates the matrix remodeling by ECs, the largest tubular lumens and the longest invading distance unexpectedly appear in hydrogels with medium plasticity instead of the highest ones. We unravel that the high plasticity of the hydrogels promotes stable integrin cluster of ECs and recruitment of focal adhesion kinase with an overenhanced contractility which downregulates the vascular endothelial cadherin expression and destabilizes the adherens junctions between individual ECs. Our results, further validated with mathematical simulations and in vivo angiogenic tests, demonstrate that a balance of matrix plasticity facilitates both cell-matrix binding and cell-to-cell adherens, for promoting vascular assembly and invasion. It is vital to unveil the effects of extracellular matrix cues on endothelial cell (EC) outgrowth for desirably governing vasculature formation, but the role of matrix plasticity on EC outgrowth is elusive. Here, the authors develop hydrogels with tunable mechanical plasticity independent of stiffness, and elucidate the plasticity-mediated responses of ECs during vasculogenesis and angiogenesis.

The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange. Three-dimensional in vitro human distal lung culture systems would strongly facilitate the investigation of pathologies such as interstitial lung disease, cancer and coronavirus disease 2019 (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we describe the development of a long-term feeder-free, chemically defined culture system for distal lung progenitors as organoids derived from single adult human alveolar epithelial type II (AT2) or KRT5 + basal cells. AT2 organoids were able to differentiate into AT1 cells, and basal cell organoids developed lumens lined with differentiated club and ciliated cells. Single-cell analysis of KRT5 + cells in basal organoids revealed a distinct population of ITGA6 + ITGB4 + mitotic cells, whose offspring further segregated into a TNFRSF12A hi subfraction that comprised about ten per cent of KRT5 + basal cells. This subpopulation formed clusters within terminal bronchioles and exhibited enriched clonogenic organoid growth activity. We created distal lung organoids with apical-out polarity to present ACE2 on the exposed external surface, facilitating infection of AT2 and basal cultures with SARS-CoV-2 and identifying club cells as a target population. This long-term, feeder-free culture of human distal lung organoids, coupled with single-cell analysis, identifies functional heterogeneity among basal cells and establishes a facile in vitro organoid model of human distal lung infections, including COVID-19-associated pneumonia. A long-term culture method for organoids derived from single adult human lung cells is used to identify progenitor cells and study SARS-CoV-2 infection.

Bamboo is a natural cellulosic material which is strongly reactive to water. Its hygroscopic behavior affects almost all other physical and mechanical properties of bamboo. This study investigated the hygroscopic swelling of moso bamboo (Phyllostachys edulis) cells in response to changes in environmental humidity using a confocal laser scanning microscope. The swelling strains of fiber, vessel and parenchyma cells were obtained and compared. The interactions between adjacent cells were also analyzed. The results demonstrated that the swelling strain of the cell walls increased with relative humidity, and was independent of its location and orientation, but dependent on the cell type. The absolute swelling of fiber cells was highest among all cells because of dominantly high fiber wall thickness. In contrast, the relative swelling of fiber cells was lowest due to constraint of adjacent fibers. Fiber cells governed the deformation and movement of other cell lumens. The difference between tangential and radial swelling of bamboo was insignificant compared to that of wood, possibly due to the similar microfibril angle in both directions, the circular cell shape and the random embedment of vascular bundles.

The villi of the human and chick gut are formed in similar stepwise progressions, wherein the mesenchyme and attached epithelium first fold into longitudinal ridges, then a zigzag pattern, and lastly individual villi. We find that these steps of vilification depend on the sequential differentiation of the distinct smooth muscle layers of the girt, which restrict the expansion of the growing endoderm and mesenchyme, generating compressive stresses that lead to their buckling and folding. A quantitative computational model, incorporating measured properties of the developing gut recapitulates the morphological patterns seen during villification in a variety of species. These results provide a mechanistic understanding of the formation of these elaborations of the lining of the gut, essential for providing sufficient surface area for nutrient absorption.