Angiogenesis InVitro: Morphogenetic and Invasive Properties of Endothelial Cells

Physiology ◽  
1990 ◽  
Vol 5 (2) ◽  
pp. 75-79
Author(s):  
R Montesano ◽  
M Pepper ◽  
L Orci
Keyword(s):  
Endothelial Cells ◽  
Animal Models ◽  
Blood Vessels ◽  
Crucial Role ◽  
Molecular Mechanisms ◽  
In Vitro Models ◽  
Capillary Blood

Angiogenesis, the formation of new capillary blood vessels, plays a crucial role in a variety of physiological and pathological processes but until recently could only be studied in animal models. Newly developed in vitro models of angiogenesis provide an opportunity for experimental dissection of molecular mechanisms of neovascularization.

Bioengineered in vitro Vascular Models for Applications in Interventional Radiology

2019 ◽  
Vol 24 (45) ◽  
pp. 5367-5374 ◽  
Author(s):  
Xiaoyun Li ◽  
Seyed M. Moosavi-Basri ◽  
Rahul Sheth ◽  
Xiaoying Wang ◽  
Yu S. Zhang
Keyword(s):  
Interventional Radiology ◽  
Animal Models ◽  
Blood Vessels ◽  
In Vitro Models ◽  
The Past ◽  
Endovascular Interventions ◽  
Conventional Animal ◽  
Vascular Structures

The role of endovascular interventions has progressed rapidly over the past several decades. While animal models have long-served as the mainstay for the advancement of this field, the use of in vitro models has become increasingly widely adopted with recent advances in engineering technologies. Here, we review the strategies, mainly including bioprinting and microfabrication, which allow for fabrication of biomimetic vascular models that will potentially serve to supplement the conventional animal models for convenient investigations of endovascular interventions. Besides normal blood vessels, those in diseased states, such as thrombosis, may also be modeled by integrating cues that simulate the microenvironment of vascular disorders. These novel engineering strategies for the development of biomimetic in vitro vascular structures will possibly enable unconventional means of studying complex endovascular intervention problems that are otherwise hard to address using existing models.

scholarly journals Radiobiological Studies of Microvascular Damage through In Vitro Models: A Methodological Perspective

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1182
Author(s):  
Luca Possenti ◽  
Laura Mecchi ◽  
Andrea Rossoni ◽  
Veronica Sangalli ◽  
Simone Bersini ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
In Vitro Models ◽  
Microvascular Endothelial Cells ◽  
Microvascular Damage ◽  
Essential Information ◽  
Reliable Model ◽  
Critical Issues ◽  
Irradiation Scheme ◽  
In Vitro Effects

Ionizing radiation (IR) is used in radiotherapy as a treatment to destroy cancer. Such treatment also affects other tissues, resulting in the so-called normal tissue complications. Endothelial cells (ECs) composing the microvasculature have essential roles in the microenvironment’s homeostasis (ME). Thus, detrimental effects induced by irradiation on ECs can influence both the tumor and healthy tissue. In-vitro models can be advantageous to study these phenomena. In this systematic review, we analyzed in-vitro models of ECs subjected to IR. We highlighted the critical issues involved in the production, irradiation, and analysis of such radiobiological in-vitro models to study microvascular endothelial cells damage. For each step, we analyzed common methodologies and critical points required to obtain a reliable model. We identified the generation of a 3D environment for model production and the inclusion of heterogeneous cell populations for a reliable ME recapitulation. Additionally, we highlighted how essential information on the irradiation scheme, crucial to correlate better observed in vitro effects to the clinical scenario, are often neglected in the analyzed studies, limiting the translation of achieved results.

Abstract 116: Arterial Endothelial Cell Has Stronger Angiogenic Potential Compared To Venous Endothelial Cell Through Up-regulation Of Endogenous FGF2 And FGF5 Expression In 3D Microfluidic System

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Ha-Rim Seo ◽  
Hyo Eun Jeong ◽  
Hyung Joon Joo ◽  
Seung-Cheol Choi ◽  
Jong-Ho Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Assay System ◽  
Vascular Density ◽  
Angiogenic Potential ◽  
Angiogenesis Assay

Background: Human body contains many kinds of different type of endothelial cells (EC). However, cellular difference of their angiogenic potential has been hardly understood. We compared in vitro angiogenic potential between arterial EC and venous EC and investigated its underlying molecular mechanisms. Method: Used human aortic endothelial cells (HAEC) which was indicated from arterial EC and human umbilical vein endothelial cells (HUVEC) indicated from venous EC. To explore angiogenic potential in detail, we adopted a novel 3D microfluidic angiogenesis assay system, which closely mimic in vivo angiogenesis. Results: In 3D microfluidic angiogenesis assay system, HAEC demonstrated stronger angiogenic potential compared to HUVEC. HAEC maintained its profound angiogenic property under different biophysical conditions. In mRNA microarray sorted on up- regulated or down-regulated genes, HAEC demonstrated significantly higher expression of gastrulation brain homeobox 2 (GBX2), fibroblast grow factor 2 (FGF2), FGF5 and collagen 8a1. Angiogenesis-related protein assay revealed that HAEC has higher secretion of endogenous FGF2 than HUVEC. HAEC has only up-regulated FGF2 and FGF5 in this part of FGF family. Furthermore, FGF5 expression under vascular endothelial growth factor-A (VEGF-A) stimulation was higher in HAEC compared to HUVEC although VEGF-A augmented FGF5 expression in both HAEC and HUVEC. Those data suggested that FGF5 expression in both HAEC and HUVEC is partially dependent to VEGF-A stimulate. HUVEC and HAEC reduced vascular density after FGF2 and FGF5 siRNA treat. Conclusion: HAEC has stronger angiogenic potential than HUVEC through up-regulation of endogenous FGF2 and FGF5 expression

scholarly journals STAT3 activation by hypoxia in in vitro models of cervix cancer and endothelial cells

Biomédica ◽  
2017 ◽  
Vol 37 (1) ◽  
pp. 119 ◽  
Author(s):  
Óscar Ortega ◽  
Alejandro Ondo-Méndez ◽  
Ruth Garzón
Keyword(s):  
Endothelial Cells ◽  
Western Blot ◽  
In Vitro Models ◽  
Cervix Cancer

Introducción. El microambiente tumoral influye en el comportamiento de las células cancerosas. Especialmente, el estímulo de agentes estresantes, como la hipoxia, se convierte en un factor crítico para la evolución y el tratamiento del cáncer. La reacción celular frente a diversos estímulos se manifiesta en la activación de vías de señalización como la JAK/STAT, una de las más importantes por sus efectos en la diferenciación y proliferación celular.Objetivo. Evaluar el estado de la vía JAK/STAT mediante la expresión o activación de la proteína STAT3 en células de cáncer de cuello uterino (HeLa) y en células endoteliales (EA.hy926) sometidas a hipoxia.Materiales y métodos. Las líneas celulares se sometieron a condiciones de hipoxia física (1 % de O2) o química (100 μM de deferoxamina, DFO) durante dos, seis y 24 horas. Mediante Western blot se determinó el cambio en la expresión y activación de STAT3, y mediante inmunofluorescencia indirecta, su localización subcelular.Resultados. La hipoxia se evidenció por la activación y translocación al núcleo del HIF-1. Ni la hipoxia física ni la química alteraron la expresión de STAT3, pero sí la activación, según se comprobó por su fosforilación y su translocación al núcleo en los dos modelos bajo estudio.Conclusiones. Se evidenció la importancia de la hipoxia como un estímulo que modifica la activación de la proteína STAT3 en las células HeLa y EA.hy926, lo cual la convierte en un elemento importante en el diseño de estrategias terapéuticas contra el cáncer.

scholarly journals Characterization of human fetal brain endothelial cells reveals barrier properties suitable for in vitro modeling of the BBB with syngenic co-cultures

2017 ◽  
Vol 38 (5) ◽  
pp. 888-903 ◽  
Author(s):  
Allison M Andrews ◽  
Evan M Lutton ◽  
Lee A Cannella ◽  
Nancy Reichenbach ◽  
Roshanak Razmpour ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Neurovascular Unit ◽  
Fetal Brain ◽  
Barrier Properties ◽  
Endothelial Activation ◽  
Fetal Tissue ◽  
In Vitro Models ◽  
Adult Brain ◽  
Alternative Source

Endothelial cells (ECs) form the basis of the blood–brain barrier (BBB), a physical barrier that selectively restricts transport into the brain. In vitro models can provide significant insight into BBB physiology, mechanisms of human disease pathology, toxicology, and drug delivery. Given the limited availability of primary human adult brain microvascular ECs ( aBMVECs), human fetal tissue offers a plausible alternative source for multiple donors and the opportunity to build syngenic tri-cultures from the same host. Previous efforts to culture fetal brain microvascular ECs ( fBMVECs) have not been successful in establishing mature barrier properties. Using optimal gestational age for isolation and flow cytometry cell sorting, we show for the first time that fBMVECs demonstrate mature barrier properties. fBMVECs exhibited similar functional phenotypes when compared to aBMVECs for barrier integrity, endothelial activation, and gene/protein expression of tight junction proteins and transporters. Importantly, we show that tissue used to culture fBMVECs can also be used to generate a syngenic co-culture, creating a microfluidic BBB on a chip. The findings presented provide a means to overcome previous challenges that limited successful barrier formation by fBMVECs. Furthermore, the source is advantageous for autologous reconstitution of the neurovascular unit for next generation in vitro BBB modeling.

scholarly journals Phospholipase Cγ Activation Drives Increased Production of Autotaxin in Endothelial Cells and Lysophosphatidic Acid-Dependent Regression

2010 ◽  
Vol 30 (10) ◽  
pp. 2401-2410 ◽  
Author(s):  
Eunok Im ◽  
Ruta Motiejunaite ◽  
Jorge Aranda ◽  
Eun Young Park ◽  
Lorenzo Federico ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Vessels ◽  
Lysophosphatidic Acid ◽  
Vascular Endothelial ◽  
Additional Mechanism ◽  
Phospholipase Cγ1 ◽  
Common Substrate ◽  
Phosphoinositide 3 Kinase ◽  
Endothelial Growth Factor

ABSTRACT We previously reported that vascular endothelial growth factor (VEGF)-dependent activation of phospholipase Cγ1 (PLCγ) regulated tube stability by competing with phosphoinositide 3-kinase (PI3K) for their common substrate. Here we describe an additional mechanism by which PLCγ promoted regression of tubes and blood vessels. Namely, it increased the level of autotaxin (ATX), which is a secreted form of lysophospholipase D that produces lysophosphatidic acid (LPA). LPA promoted motility of endothelial cells, leading to disorganization/regression of tubes in vitro. Furthermore, mice that under- or overexpressed members of this intrinsic destabilization pathway showed either delayed or accelerated, respectively, regression of blood vessels. We conclude that endothelial cells can be instructed to engage a PLCγ-dependent intrinsic destabilization pathway that results in the production of soluble regression factors such as ATX and LPA. These findings are likely to potentiate ongoing efforts to prevent, manage, and eradicate numerous angiogenesis-based diseases such as proliferative diabetic retinopathy and solid tumors.

scholarly journals Molecular Aspects of Varicella-Zoster Virus Latency

2018 ◽  
Author(s):  
Daniel P. Depledge ◽  
Tomohiko Sadaoka ◽  
Werner J. D. Ouwendijk
Keyword(s):  
Varicella Zoster Virus ◽  
Molecular Mechanisms ◽  
Neurological Complications ◽  
In Vitro Models ◽  
New Era ◽  
Varicella Zoster ◽  
Virus Latency ◽  
Technological Advances ◽  
Molecular Aspects

Primary varicella-zoster virus (VZV) infection causes varicella (chickenpox) and the establishment of a lifelong latent infection in ganglionic neurons. VZV reactivates in about one-third of infected individuals to cause herpes zoster, often accompanied by neurological complications. The restricted host range of VZV and, until recently, the lack of suitable in vitro models to study VZV latency have seriously hampered molecular studies of viral latency. Nevertheless, recent technological advances facilitated a series of exciting studies that resulted in the discovery of a VZV latency-associated transcript (VLT) and have redefined our understanding of VZV latency and factors that initiate reactivation. Together, these findings pave the way for a new era of research that may finally unravel the precise molecular mechanisms that govern latency. In this review, we will summarize the implications of recent discoveries in the VZV latency field from both a virus and host perspective and provide a roadmap for future studies.

scholarly journals Diabetic Endothelial Cells Differentiated From Patient iPSCs Show Dysregulated Glycine Homeostasis and Senescence Associated Phenotypes

2021 ◽  
Vol 9 ◽  
Author(s):  
Liping Su ◽  
Xiaocen Kong ◽  
Sze Jie Loo ◽  
Yu Gao ◽  
Jean-Paul Kovalik ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Pluripotent Stem Cells ◽  
Molecular Mechanisms ◽  
Cell Transfer ◽  
Angiogenic Potential ◽  
Patients With Diabetes ◽  
Induced Pluripotent

Induced pluripotent stem cells derived cells (iPSCs) not only can be used for personalized cell transfer therapy, but also can be used for modeling diseases for drug screening and discovery in vitro. Although prior studies have characterized the function of rodent iPSCs derived endothelial cells (ECs) in diabetes or metabolic syndrome, feature phenotypes are largely unknown in hiPSC-ECs from patients with diabetes. Here, we used hiPSC lines from patients with type 2 diabetes mellitus (T2DM) and differentiated them into ECs (dia-hiPSC-ECs). We found that dia-hiPSC-ECs had disrupted glycine homeostasis, increased senescence, and impaired mitochondrial function and angiogenic potential as compared with healthy hiPSC-ECs. These signature phenotypes will be helpful to establish dia-hiPSC-ECs as models of endothelial dysfunction for understanding molecular mechanisms of disease and for identifying and testing new targets for the treatment of endothelial dysfunction in diabetes.

scholarly journals Human iPSC-derived mesodermal progenitor cells preserve their vasculogenesis potential after extrusion and form hierarchically organized blood vessels

2021 ◽  
Author(s):  
Leyla Dogan ◽  
Ruben Scheuring ◽  
Nicole Wagner ◽  
Yuichiro Ueda ◽  
Philipp Woersdoerfer ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Vessels ◽  
Progenitor Cells ◽  
Vessel Wall ◽  
De Novo ◽  
Hierarchical Organization ◽  
Wall Structure ◽  
Electron Microscopic ◽  
Vessel Formation

Post-fabrication formation of a proper vasculature remains an unresolved challenge in bioprinting. Established strategies focus on the supply of the fabricated structure with nutrients and oxygen and either rely on the mere formation of a channel system using fugitive inks, or additionally use mature endothelial cells and/or peri-endothelial cells such as smooth muscle cells for the formation of blood vessels in vitro. Functional vessels, however, exhibit a hierarchical organization and multilayered wall structure that is important for their function. Human induced pluripotent stem cell-derived mesodermal progenitor cells (hiMPCs) have been shown to possess the capacity to form blood vessels in vitro, but have so far not been assessed for their applicability in bioprinting processes. Here, we demonstrate that hiMPCs, after formulation into an alginate/collagen type 1 bioink and subsequent extrusion, retain their ability to give rise to the formation of complex vessels that display a hierarchical network in a process that mimicks the embryonic steps of vessel formation by vasculogenesis. Histological evaluations at different time points of extrusion revealed initial formation of spheres, followed by lumen formation and further structural maturation as evidenced by building a multilayered vessel wall and a vascular network. These findings are supported by immunostainings for endothelial and peri-endothelial cell markers as well as electron microscopic analyses at the ultrastructural level. Moreover, capillary-like vessel structures deposited a basement membrane-like matrix structure at the basal side between the vessel wall and the alginate-collagen matrix. These results evidence the applicability and great potential of hiMPCs for the bioprinting of vascular structures mimicking the basic morphogenetic steps of de novo vessel formation during embryogenesis.

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