Transcribing In Vivo Blood Vessel Networks into In Vitro Perfusable Microfluidic Devices

2020 ◽  
Vol 5 (6) ◽  
pp. 2000103 ◽  
Author(s):  
Yih Yang Chen ◽  
Benjamin R. Kingston ◽  
Warren C. W. Chan
Keyword(s):  
Blood Vessel ◽  
Microfluidic Devices ◽  
Vessel Networks

scholarly journals Image-based modelling of skeletal muscle oxygenation

2017 ◽  
Vol 14 (127) ◽  
pp. 20160992 ◽  
Author(s):  
B. Zeller-Plumhoff ◽  
T. Roose ◽  
G. F. Clough ◽  
P. Schneider
Keyword(s):  
Skeletal Muscle ◽  
Blood Vessel ◽  
Ex Vivo ◽  
Imaging Techniques ◽  
Muscle Oxygenation ◽  
Skeletal Muscle Oxygenation ◽  
Health And Disease ◽  
Vessel Networks

The supply of oxygen in sufficient quantity is vital for the correct functioning of all organs in the human body, in particular for skeletal muscle during exercise. Disease is often associated with both an inhibition of the microvascular supply capability and is thought to relate to changes in the structure of blood vessel networks. Different methods exist to investigate the influence of the microvascular structure on tissue oxygenation, varying over a range of application areas, i.e. biological in vivo and in vitro experiments, imaging and mathematical modelling. Ideally, all of these methods should be combined within the same framework in order to fully understand the processes involved. This review discusses the mathematical models of skeletal muscle oxygenation currently available that are based upon images taken of the muscle microvasculature in vivo and ex vivo . Imaging systems suitable for capturing the blood vessel networks are discussed and respective contrasting methods presented. The review further informs the association between anatomical characteristics in health and disease. With this review we give the reader a tool to understand and establish the workflow of developing an image-based model of skeletal muscle oxygenation. Finally, we give an outlook for improvements needed for measurements and imaging techniques to adequately investigate the microvascular capability for oxygen exchange.

scholarly journals Rapid Fabrication of Microfluidic Devices for Biological Mimicking: A Survey of Materials and Biocompatibility

Micromachines ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 346
Author(s):  
Hui Ling Ma ◽  
Ana Carolina Urbaczek ◽  
Fayene Zeferino Ribeiro de Souza ◽  
Paulo Augusto Gomes Garrido Carneiro Leão ◽  
Janice Rodrigues Perussi ◽  
...  
Keyword(s):  
Shear Stress ◽  
Cell Viability ◽  
Cellular Response ◽  
Fluid Shear Stress ◽  
Umbilical Vein ◽  
Microfluidic Devices ◽  
In Vitro Assays ◽  
Stress Effect

Microfluidics is an essential technique used in the development of in vitro models for mimicking complex biological systems. The microchip with microfluidic flows offers the precise control of the microenvironment where the cells can grow and structure inside channels to resemble in vivo conditions allowing a proper cellular response investigation. Hence, this study aimed to develop low-cost, simple microchips to simulate the shear stress effect on the human umbilical vein endothelial cells (HUVEC). Differentially from other biological microfluidic devices described in the literature, we used readily available tools like heat-lamination, toner printer, laser cutter and biocompatible double-sided adhesive tapes to bind different layers of materials together, forming a designed composite with a microchannel. In addition, we screened alternative substrates, including polyester-toner, polyester-vinyl, glass, Permanox® and polystyrene to compose the microchips for optimizing cell adhesion, then enabling these microdevices when coupled to a syringe pump, the cells can withstand the fluid shear stress range from 1 to 4 dyne cm2. The cell viability was monitored by acridine orange/ethidium bromide (AO/EB) staining to detect live and dead cells. As a result, our fabrication processes were cost-effective and straightforward. The materials investigated in the assembling of the microchips exhibited good cell viability and biocompatibility, providing a dynamic microenvironment for cell proliferation. Therefore, we suggest that these microchips could be available everywhere, allowing in vitro assays for daily laboratory experiments and further developing the organ-on-a-chip concept.

scholarly journals O23: CHARACTERISING PATIENT-DERIVED COLORECTAL CANCER TISSUE-ORIGINATED ORGANOIDAL SPHEROIDS FOR HIGH-THROUGHPUT MICROFLUIDIC APPLICATIONS

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
MI Khot ◽  
M Levenstein ◽  
R Coppo ◽  
J Kondo ◽  
M Inoue ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fluid Flow ◽  
High Throughput ◽  
Microfluidic Devices ◽  
In Vitro Models ◽  
Fluorescent Imaging ◽  
Cancer Tissue ◽  
Cell Models

Abstract Introduction Three-dimensional (3D) cell models have gained reputation as better representations of in vivo cancers as compared to monolayered cultures. Recently, patient tumour tissue-derived organoids have advanced the scope of complex in vitro models, by allowing patient-specific tumour cultures to be generated for developing new medicines and patient-tailored treatments. Integrating 3D cell and organoid culturing into microfluidics, can streamline traditional protocols and allow complex and precise high-throughput experiments to be performed with ease. Method Patient-derived colorectal cancer tissue-originated organoidal spheroids (CTOS) cultures were acquired from Kyoto University, Japan. CTOS were cultured in Matrigel and stem-cell media. CTOS were treated with 5-fluorouracil and cytotoxicity evaluated via fluorescent imaging and ATP assay. CTOS were embedded, sectioned and subjected to H&E staining and immunofluorescence for ABCG2 and Ki67 proteins. HT29 colorectal cancer spheroids were produced on microfluidic devices using cell suspensions and subjected to 5-fluorouracil treatment via fluid flow. Cytotoxicity was evaluated through fluorescent imaging and LDH assay. Result 5-fluorouracil dose-dependent reduction in cell viability was observed in CTOS cultures (p<0.01). Colorectal CTOS cultures retained the histology, tissue architecture and protein expression of the colonic epithelial structure. Uniform 3D HT29 spheroids were generated in the microfluidic devices. 5-fluorouracil treatment of spheroids and cytotoxic analysis was achieved conveniently through fluid flow. Conclusion Patient-derived CTOS are better complex models of in vivo cancers than 3D cell models and can improve the clinical translation of novel treatments. Microfluidics can streamline high-throughput screening and reduce the practical difficulties of conventional organoid and 3D cell culturing. Take-home message Organoids are the most advanced in vitro models of clinical cancers. Microfluidics can streamline and improve traditional laboratory experiments.

In Vivo and In Vitro Cytotoxicity of Brown Spider Venom for Blood Vessel Endothelial Cells

2001 ◽  
Vol 102 (3) ◽  
pp. 229-237 ◽  
Author(s):  
Silvio S Veiga ◽  
Vera C Zanetti ◽  
Celia R.C Franco ◽  
Edvaldo S Trindade ◽  
Marimelia A Porcionatto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Vessel ◽  
In Vitro Cytotoxicity ◽  
Spider Venom ◽  
Brown Spider

scholarly journals A microfluidic platform for cultivating ovarian cancer spheroids and testing their responses to chemotherapies

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Neda Dadgar ◽  
Alan M. Gonzalez-Suarez ◽  
Pouria Fattahi ◽  
Xiaonan Hou ◽  
John S. Weroha ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Drug Testing ◽  
Microfluidic Devices ◽  
Needle Aspiration ◽  
High Concentration ◽  
Microfluidic Platform ◽  
Drug Concentrations

Abstract There is increasing interest in utilizing in vitro cultures as patient avatars to develop personalized treatment for cancer. Typical cultures utilize Matrigel-coated plates and media to promote the proliferation of cancer cells as spheroids or tumor explants. However, standard culture conditions operate in large volumes and require a high concentration of cancer cells to initiate this process. Other limitations include variability in the ability to successfully establish a stable line and inconsistency in the dimensions of these microcancers for in vivo drug response measurements. This paper explored the utility of microfluidics in the cultivation of cancer cell spheroids. Six patient-derived xenograft (PDX) tumors of high-grade serous ovarian cancer were used as the source material to demonstrate that viability and epithelial marker expression in the microfluidic cultures was superior to that of Matrigel or large volume 3D cultures. To further demonstrate the potential for miniaturization and multiplexing, we fabricated multichamber microfluidic devices with integrated microvalves to enable serial seeding of several chambers followed by parallel testing of several drug concentrations. These valve-enabled microfluidic devices permitted the formation of spheroids and testing of seven drug concentrations with as few as 100,000 cancer cells per device. Overall, we demonstrate the feasibility of maintaining difficul-to-culture primary cancer cells and testing drugs in a microfluidic device. This microfluidic platform may be ideal for drug testing and personalized therapy when tumor material is limited, such as following the acquisition of biopsy specimens obtained by fine-needle aspiration.

Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall

Blood ◽  
2005 ◽  
Vol 105 (1) ◽  
pp. 192-198 ◽  
Author(s):  
Sharlene M. Day ◽  
Jennifer L. Reeve ◽  
Brian Pedersen ◽  
Diana M Farris ◽  
Daniel D. Myers ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Tissue Factor ◽  
Vessel Wall ◽  
Thrombus Formation ◽  
Vena Cava ◽  
Vascular Wall ◽  
Blood Vessel Wall ◽  
Wild Type

Abstract Leukocytes and leukocyte-derived microparticles contain low levels of tissue factor (TF) and incorporate into forming thrombi. Although this circulating pool of TF has been proposed to play a key role in thrombosis, its functional significance relative to that of vascular wall TF is poorly defined. We tested the hypothesis that leukocyte-derived TF contributes to thrombus formation in vivo. Compared to wild-type mice, mice with severe TF deficiency (ie, TF–/–, hTF-Tg+, or “low-TF”) demonstrated markedly impaired thrombus formation after carotid artery injury or inferior vena cava ligation. A bone marrow transplantation strategy was used to modulate levels of leukocyte-derived TF. Transplantation of low-TF marrow into wild-type mice did not suppress arterial or venous thrombus formation. Similarly, transplantation of wild-type marrow into low-TF mice did not accelerate thrombosis. In vitro analyses revealed that TF activity in the blood was very low and was markedly exceeded by that present in the vessel wall. Therefore, our results suggest that thrombus formation in the arterial and venous macrovasculature is driven primarily by TF derived from the blood vessel wall as opposed to leukocytes.

Silole-Based Red Fluorescent Organic Dots for Bright Two-Photon Fluorescence In vitro Cell and In vivo Blood Vessel Imaging

Small ◽  
2015 ◽  
Vol 12 (6) ◽  
pp. 782-792 ◽  
Author(s):  
Bin Chen ◽  
Guangxue Feng ◽  
Bairong He ◽  
Chiching Goh ◽  
Shidang Xu ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Two Photon ◽  
Vessel Imaging ◽  
Two Photon Fluorescence ◽  
Photon Fluorescence

MODIFIED ALGINATE/CHITOSAN HOLLOW MICROFIBER AS A BIOCOMPATIBLE FRAME FOR BLOOD VESSEL RECONSTRUCTION

Nano LIFE ◽  
2012 ◽  
Vol 02 (04) ◽  
pp. 1242005 ◽  
Author(s):  
XULANG ZHANG ◽  
JIANHUA QIN
Keyword(s):  
Blood Vessel ◽  
Hollow Fiber ◽  
Vascular Tissue ◽  
Umbilical Vein ◽  
Fiber Surface ◽  
Cell Capture ◽  
Umbilical Vein Endothelial Cells ◽  
Vessel Reconstruction

We presented a new approach to produce Chitosan–Glutaraldehyde–Chitosan–Alginate (CGCA) hollow fiber with the capability of cell capture and adhesion for vascular tissue engineering. The CGCA hollow fiber was generated by sacrificing the inner part of alginate/chitosan (A/C) solid fiber using sodium citrate, followed by glutaraldehyde (GA) cross-linking chitosan to form stable imine bonds on the fiber surface. Furthermore, human umbilical vein endothelial cells (HUVEC) were captured by the CGCA hollow fiber surface and adhesive as layer pattern with good viability and normal morphology. This strategy facilitated the lumen structure formation with good biocompatibility by biomaterials modification, providing a promising and facile technique for blood vessel regeneration in vitro and in vivo.

Hypoxia induces capillary network formation in cultured bovine pulmonary microvessel endothelial cells

1995 ◽  
Vol 268 (5) ◽  
pp. L789-L800 ◽  
Author(s):  
P. G. Phillips ◽  
L. M. Birnby ◽  
A. Narendran
Keyword(s):  
In Vitro Model ◽  
Network Formation ◽  
Collagen Gel ◽  
Coronary Artery Occlusion ◽  
In Vivo Studies ◽  
Hypoxic Exposure ◽  
Vitro Model ◽  
Vessel Networks

The development of new vessels (angiogenesis) is essential to wound healing. The center of a wound space is hypoxic, a condition that has been shown to stimulate angiogenesis in animal models of coronary artery occlusion. Because the mechanisms involved in this complex process are difficult to study in situ, an in vitro model would provide a useful complement to in vivo studies. This laboratory has developed and characterized calf pulmonary microvessel endothelial cell (PMVEC) cultures and an in vitro model system of angiogenesis using collagen three-dimensional gels that permit migration of cells into vessel networks. This system was used to study the direct effect of normoxia (20% O2) or hypoxia (5% O2) on PMVEC ability to undergo angiogenesis in vitro. Major changes leading to formation of capillary-like networks occurred during the first 3 days of hypoxic exposure only and included restructuring of actin filament networks, focal changes in distribution of basic fibroblast growth factor, and orientation and migration of cell tracts into a collagen gel matrix to form vessel networks.

Myricetin-Based Self-Assembled Nanoparticles for Tumor Synergistic Therapy by Antioxidation Pathway

2021 ◽  
Vol 17 (12) ◽  
pp. 2399-2412
Author(s):  
Yumei Qian ◽  
Fang Zhao ◽  
Jing Wang ◽  
Hongxia Li ◽  
Lisheng Xu ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Vascular Endothelial ◽  
Ferric Ions ◽  
Normal Cells ◽  
Hypoxia Inducible Factor 1 ◽  
Self Assembled ◽  
Vessel Networks ◽  
Endothelial Growth Factor

Nanoplatforms are nano-scale systems that can transport different small molecular anticancer drugs or chemosensitization motif to accumulate in tumor cells without obvious side-effect in normal cells and achieve a synergistic therapy. In this paper the new self-assembled nanoparticles (NPs) merging doxorubicin (DOX) and myricetin (MYR) with ferric ions (Fe3+) and polyphenol was employed for forming the DOX@MYR-Fe3+ NP (FDMP NP). The FDMP NPs could reduce the DOX-induced toxicity in blood; and they could not cause damage to the heart and kidney tissues by the reasons that the MYR could enhance the anti-oxidation capability in normal cells, which resulted in preventing ROS-induced damage. Additionally, the FDMP NPs were characteristic of small size (37.70 ± 6.30 nm), high DOX loading efficiency (46.67 ± 1.58%), pH-controlled release and excellent stable pharmacokinetics, that inducing drug release and enhancing drug accumulation in the tumor. Moreover, the FDMP NPs could inhibit the expression of the hypoxia-inducible factor-1 α(HIF-1α) and the key angiogenesis mediator vascular endothelial growth factor (VEGF) both in vitro and in vivo, which succeed in preventing the generation of new blood vessel networks; that is the mechanism of the synergistic effect against tumors induced by FDMP NPs.

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