“Open-top” microfluidic device for in vitro three-dimensional capillary beds

Lab on a Chip ◽  
2017 ◽  
Vol 17 (20) ◽  
pp. 3405-3414 ◽  
Author(s):  
Soojung Oh ◽  
Hyunryul Ryu ◽  
Dongha Tahk ◽  
Jihoon Ko ◽  
Yoojin Chung ◽  
...  

We introduce a novel microfluidic device to co-culture a blood vessel network and cell tissues in an in vivo-like niche.

Lab on a Chip ◽  
2015 ◽  
Vol 15 (17) ◽  
pp. 3521-3529 ◽  
Author(s):  
Luis F. Alonzo ◽  
Monica L. Moya ◽  
Venktesh S. Shirure ◽  
Steven C. George

To address the gap between in vivo microenvironments and in vitro systems, we have developed a novel microfluidic device that precisely controls the spatial and temporal interactions between adjacent three-dimensional cellular environments.


2018 ◽  
Author(s):  
Beatriz Garcia-Diaz ◽  
Corinne Bachelin ◽  
Fanny Coulpier ◽  
Gaspard Gerschenfeld ◽  
Cyrille Deboux ◽  
...  

ABSTRACTSchwann cells (SC) enter the central nervous system (CNS) in pathophysiological conditions. However, how SC invade the CNS to remyelinate central axons remains undetermined. We studied SC migratory behaviorex vivoandin vivoafter exogenous transplantation in the demyelinated spinal cord. Data highlight for the first time that SC migrate preferentially along blood vessel in perivascular ECM, avoiding CNS myelin. We demonstratein vitroandin vivothat this migration route occurs by virtue of a dual mode of action of Eph/ephrin receptor. Indeed, EphrinB3, enriched in myelin, interacts with SC Eph receptors, to drive SC away from CNS myelin, and triggers their preferential adhesion to ECM components, such as fibronectin via integrinβ1 interactions. This complex interplay enhances SC migration along the blood vessel network and together with lesion-induced vascular remodeling facilitates their timely invasion of the lesion site. These novel findings elucidate the mechanism by which SC invade and contribute to spinal cord repair.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Robin M. H. Rumney ◽  
Stuart A. Lanham ◽  
Janos M. Kanczler ◽  
Alexander P. Kao ◽  
Lalitha Thiagarajan ◽  
...  

AbstractDeficient bone vasculature is a key component in pathological conditions ranging from developmental skeletal abnormalities to impaired bone repair. Vascularisation is dependent upon vascular endothelial growth factor (VEGF), which drives both angiogenesis and osteogenesis. The aim of this study was to examine the efficacy of blood vessel and bone formation following transfection with VEGF RNA or delivery of recombinant human VEGF165 protein (rhVEGF165) across in vitro and in vivo model systems. To quantify blood vessels within bone, an innovative approach was developed using high-resolution X-ray computed tomography (XCT) to generate quantifiable three-dimensional reconstructions. Application of rhVEGF165 enhanced osteogenesis, as evidenced by increased human osteoblast-like MG-63 cell proliferation in vitro and calvarial bone thickness following in vivo administration. In contrast, transfection with VEGF RNA triggered angiogenic effects by promoting VEGF protein secretion from MG-63VEGF165 cells in vitro, which resulted in significantly increased angiogenesis in the chorioallantoic (CAM) assay in ovo. Furthermore, direct transfection of bone with VEGF RNA in vivo increased intraosseous vascular branching. This study demonstrates the importance of continuous supply as opposed to a single high dose of VEGF on angiogenesis and osteogenesis and, illustrates the potential of XCT in delineating in 3D, blood vessel connectivity in bone.


2017 ◽  
Author(s):  
James A. Grogan ◽  
Anthony J. Connor ◽  
Joe M. Pitt-Francis ◽  
Philip K. Maini ◽  
Helen M. Byrne

AbstractThe corneal micropocket angiogenesis assay is an experimental protocol for studying vessel network formation, or neovascularization, in vivo. The assay is attractive due to the ease with which the developing vessel network can be observed in the same animal over time. Measurements from the assay have been used in combination with mathematical modeling to gain insights into the mechanisms of angiogenesis. While previous modeling studies have adopted planar domains to represent the assay, the hemispherical shape of the cornea and asymmetric positioning of the angiogenic source can be seen to affect vascular patterning in experimental images. As such, we aim to better understand: i) how the geometry of the assay influences vessel network formation and ii) how to relate observations from planar domains to those in the hemispherical cornea. To do so, we develop a three-dimensional, off-lattice mathematical model of neovascularization in the cornea, using a spatially resolved representation of the assay for the first time. Relative to the detailed model, we predict that the adoption of planar geometries has a noticeable impact on vascular patterning, leading to increased vessel ‘merging’, or anastomosis, in particular when circular geometries are adopted. Significant differences in the dynamics of diffusible aniogenesis simulators are also predicted between different domains. In terms of comparing predictions across domains, the ‘distance of the vascular front to the limbus’ metric is found to have low sensitivity to domain choice, while metrics such as densities of tip cells and vessels and ‘vascularized fraction’ are sensitive to domain choice. Given the widespread adoption and attractive simplicity of planar tissue domains, both in silico and in vitro, the differences identified in the present study should prove useful in relating the results of previous and future theoretical studies of neovascularization to in vivo observations in the cornea.Author summaryNeovascularization, or the formation of new blood vessels, is an important process in development, wound healing and cancer. The corneal micropocket assay is used to better understand the process and, in the case of cancer, how it can be controlled with drug therapies for improved patient outcomes. In the assay, the hemispherical shape of the cornea can influence the way the vessel network forms. This makes it difficult to directly compare results from experiments with the predictions of mathematical models or cell culture experiments, which are typically performed on flat substrates or planar matrices. In this study, we use mathematical modeling to investigate how the hemispherical shape of the cornea affects vessel formation and to identify how sensitive different measurements of neovascularization are to geometry.


Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.


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