scholarly journals Synthetic extracellular matrices with tailored adhesiveness and degradability support lumen formation during angiogenic sprouting

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jifeng Liu ◽  
Hongyan Long ◽  
Dagmar Zeuschner ◽  
Andreas F. B. Räder ◽  
William J. Polacheck ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Material Properties ◽  
In Vitro Model ◽  
Matrix Remodeling ◽  
Lumen Formation ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Vitro Model ◽  
Cell Matrix Interactions

AbstractA major deficit in tissue engineering strategies is the lack of materials that promote angiogenesis, wherein endothelial cells from the host vasculature invade the implanted matrix to form new blood vessels. To determine the material properties that regulate angiogenesis, we have developed a microfluidic in vitro model in which chemokine-guided endothelial cell sprouting into a tunable hydrogel is followed by the formation of perfusable lumens. We show that long, perfusable tubes only develop if hydrogel adhesiveness and degradability are fine-tuned to support the initial collective invasion of endothelial cells and, at the same time, allow for matrix remodeling to permit the opening of lumens. These studies provide a better understanding of how cell-matrix interactions regulate angiogenesis and, therefore, constitute an important step towards optimal design criteria for tissue-engineered materials that require vascularization.

scholarly journals Best Practices and Progress in Precision-Cut Liver Slice Cultures

2021 ◽  
Vol 22 (13) ◽  
pp. 7137
Author(s):  
Liza Dewyse ◽  
Hendrik Reynaert ◽  
Leo A. van Grunsven
Keyword(s):  
Liver Disease ◽  
In Vitro Model ◽  
Liver Slice ◽  
In Vitro Models ◽  
Promising Tool ◽  
Cell Matrix ◽  
Vitro Model ◽  
Cell Matrix Interactions

Thirty-five years ago, precision-cut liver slices (PCLS) were described as a promising tool and were expected to become the standard in vitro model to study liver disease as they tick off all characteristics of a good in vitro model. In contrast to most in vitro models, PCLS retain the complex 3D liver structures found in vivo, including cell–cell and cell–matrix interactions, and therefore should constitute the most reliable tool to model and to investigate pathways underlying chronic liver disease in vitro. Nevertheless, the biggest disadvantage of the model is the initiation of a procedure-induced fibrotic response. In this review, we describe the parameters and potential of PCLS cultures and discuss whether the initially described limitations and pitfalls have been overcome. We summarize the latest advances in PCLS research and critically evaluate PCLS use and progress since its invention in 1985.

scholarly journals Generation of a Novel In Vitro Model to Study Endothelial Dysfunction from Atherothrombotic Specimens

2021 ◽  
Author(s):  
Susan Gallogly ◽  
Takeshi Fujisawa ◽  
John D. Hung ◽  
Mairi Brittan ◽  
Elizabeth M. Skinner ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
In Vitro Model ◽  
Umbilical Vein ◽  
Coronary Syndrome ◽  
Coronary Endothelial Cells ◽  
Vitro Model ◽  
Umbilical Vein Endothelial Cells

Abstract Purpose Endothelial dysfunction is central to the pathogenesis of acute coronary syndrome. The study of diseased endothelium is very challenging due to inherent difficulties in isolating endothelial cells from the coronary vascular bed. We sought to isolate and characterise coronary endothelial cells from patients undergoing thrombectomy for myocardial infarction to develop a patient-specific in vitro model of endothelial dysfunction. Methods In a prospective cohort study, 49 patients underwent percutaneous coronary intervention with thrombus aspiration. Specimens were cultured, and coronary endothelial outgrowth (CEO) cells were isolated. CEO cells, endothelial cells isolated from peripheral blood, explanted coronary arteries, and umbilical veins were phenotyped and assessed functionally in vitro and in vivo. Results CEO cells were obtained from 27/37 (73%) atherothrombotic specimens and gave rise to cells with cobblestone morphology expressing CD146 (94 ± 6%), CD31 (87 ± 14%), and von Willebrand factor (100 ± 1%). Proliferation of CEO cells was impaired compared to both coronary artery and umbilical vein endothelial cells (population doubling time, 2.5 ± 1.0 versus 1.6 ± 0.3 and 1.2 ± 0.3 days, respectively). Cell migration was also reduced compared to umbilical vein endothelial cells (29 ± 20% versus 85±19%). Importantly, unlike control endothelial cells, dysfunctional CEO cells did not incorporate into new vessels or promote angiogenesis in vivo. Conclusions CEO cells can be reliably isolated and cultured from thrombectomy specimens in patients with acute coronary syndrome. Compared to controls, patient-derived coronary endothelial cells had impaired capacity to proliferate, migrate, and contribute to angiogenesis. CEO cells could be used to identify novel therapeutic targets to enhance endothelial function and prevent acute coronary syndromes.

Platelets and Endothelial Cells Act in Concert to Delay Thrombolysis – Evidence from an In Vitro Model of the Human Occlusive Thrombus

1998 ◽  
Vol 79 (03) ◽  
pp. 602-608 ◽  
Author(s):  
W. G. Jerome ◽  
S. Handt ◽  
R. R. Hantgan
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
In Vitro Model ◽  
Umbilical Vein ◽  
Plasminogen Activator Inhibitor ◽  
Genetically Engineered ◽  
Cellular Mechanisms ◽  
Vitro Model ◽  
Activator Inhibitor

SummaryThe molecular and cellular mechanisms that over a period of hours render a human thrombus progressively resistant to fibrinolysis have been probed with a novel in vitro model. The kinetics of clot formation and fibrinolysis were monitored by laser light scattering with platelet-rich model thrombi contained in cylindrical flow chambers. In selected experiments, human umbilical vein endothelial cells were also cultured to confluence on the inner walls of these “glass blood vessels”. Following an “aging” period (0.5, 2 or 4 h), each thrombus was gently perfused with a bolus of plasminogen/recombinant tissue plasminogen activator to induce fibrinolysis. Platelets delayed lysis of 2 h-aged thrombi by ~70% and (non-stimulated) endothelial cells by ~30%, compared to cell-free control clots. However, even greater lytic delays (~260%) resulted when both vascular cells were present in the same 2 h-aged thrombus. In contrast, rapid lysis was consistently achieved with R298E,R299E t-PA, a genetically engineered plasminogen activator that is insensitive to inhibition by plasminogen activator inhibitor type 1. These observations suggest platelets and endothelial cells act in concert to enrich the fibrin scaffold of an aging human thrombus in plasminogen activator inhibitor. We propose that the presence of both platelets and endothelial cells may contribute to progressive thrombolytic resistance.

Venular endothelial cells from bovine heart

1988 ◽  
Vol 254 (6) ◽  
pp. H1211-H1217 ◽  
Author(s):  
M. E. Schelling ◽  
C. J. Meininger ◽  
J. R. Hawker ◽  
H. J. Granger
Keyword(s):  
Endothelial Cells ◽  
In Vitro Model ◽  
Protein Transport ◽  
Culture Conditions ◽  
Support Cell ◽  
Vitro Model ◽  
Microvascular Cells ◽  
Selection Of ◽  
Coronary Angiogenesis

Coronary venular endothelial cells were isolated by a bead-perfusion technique that allowed the selection of endothelial cells from venules of a specific size. Culture conditions for the microvascular cells were established. Cells grew well in supplemented Dulbecco's modified Eagle's medium. The effect of various substrata on the proliferation of the venular endothelial cells was determined. Matrigel, gelatin, and fibronectin supported high levels of proliferation. Cell shape was correlated with ability of the substratum to support cell proliferation. Cells exhibiting a broad, flattened morphology achieved high levels of proliferation. The formation of vessel meshworks by the coronary venular endothelial cells provides an in vitro model for the study of coronary angiogenesis. Confluent monolayers of these cells can be utilized to examine mechanisms of water and protein transport across coronary venules.

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