Developing a xenograft model of human vasculature in the mouse ear pinna

Meehan, Gavin R.; Scales, Hannah E.; Osii, Rowland; Niz, Mariana De; Lawton, Jennifer; Marti, Matthias; Garside, Paul; Craig, Alister G.; Brewer, James M.

doi:10.1038/s41598-020-58650-y

Cited by 7 publications

(5 citation statements)

References 44 publications

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“…in vivo, we tested the commercially available fluorescently-labeled antibody CD31 that recognizes human ECs 14 , and confirmed its species specificity using human ECs HUVECs and mouse ECs MS-1 cells. We tested Alexa Fluor 488-conjugated human CD31 antibody (huCD31-AF488 Ab) and Alexa Fluor 647-conjugated mouse CD31 antibody (moCD31-AF647Ab).…”

Section: Confirmation Of Specific Recognition Of Human Ecs To Distinmentioning

confidence: 86%

An in vivo model allowing continuous observation of human vascular formation in the same animal over time

Tsukada

Muramatsu

Hayashi

et al. 2021

Sci Rep

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Angiogenesis contributes to numerous pathological conditions. Understanding the molecular mechanisms of angiogenesis will offer new therapeutic opportunities. Several experimental in vivo models that better represent the pathological conditions have been generated for this purpose in mice, but it is difficult to translate results from mouse to human blood vessels. To understand human vascular biology and translate findings into human research, we need human blood vessel models to replicate human vascular physiology. Here, we show that human tumor tissue transplantation into a cranial window enables engraftment of human blood vessels in mice. An in vivo imaging technique using two-photon microscopy allows continuous observation of human blood vessels until at least 49 days after tumor transplantation. These human blood vessels make connections with mouse blood vessels as shown by the finding that lectin injected into the mouse tail vein reaches the human blood vessels. Finally, this model revealed that formation and/or maintenance of human blood vessels depends on VEGFR2 signaling. This approach represents a useful tool to study molecular mechanisms of human blood vessel formation and to test effects of drugs that target human blood vessels in vivo to show proof of concept in a preclinical model.

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Section: Confirmation Of Specific Recognition Of Human Ecs To Distinmentioning

confidence: 86%

An in vivo model allowing continuous observation of human vascular formation in the same animal over time

Tsukada

Muramatsu

Hayashi

et al. 2021

Sci Rep

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“…This is the case that can be found in some artificial implants where a large vasculature is aimed to be developed [60].…”

Section: Case 2: Angiogenesis In a Large And Plane Surfacementioning

confidence: 90%

A simple agent-based model to simulate 3D tumor-induced angiogenesis considering the evolution of the hypoxic conditions of the cells

Benítez

García-Mozos

Santos

et al. 2022

Engineering with Computers

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In tumors, angiogenesis (conformation of a new vasculature from another primal one) is produced with the releasing of tumor angiogenic factors from hypoxic cells. These angiogenic substances are distributed around the tumor micro-environment by diffusion. When they reach the primal blood vessel bed, the sprouting and branching of a new micro-vascular network is produced. These new capillaries will supply oxygen to cells so that their hypoxic state is overcome. In this work, a new and simple 3D agent-based model to simulate tumor-induced angiogenesis is presented. In this approach, the evolution of the hypoxic conditions in cells along the related conformation of the new micro-vessels is considered. The importance that the relative position of the primal vasculature and tumor structure takes in the final distribution of the new micro-vasculature has also been addressed. The diffusion of angiogenic factors and oxygen has been modelled at the targets by numerical convolution superposition of the analytical solution from the sources. Qualitative and quantitative results show the importance of tip endothelial cells in overcoming hypoxic conditions in cells at early stages of angiogenesis. At final stages, anastomosis plays an important role in the reduction of hypoxia in cells.

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“…From clinical studies and in vitro research, it seems likely that contributions to pathology come from many different factors, including the location of sequestered infected erythrocytes, reduction in vascular flow, host inflammation and endothelial dysfunction caused by the presence and rupture of infected erythrocytes. Models of malaria cytoadherence can help by providing supporting data on endothelial responses to a range of components derived from IE adhesion or locally released factors, and some of these models have become quite sophisticated [ 87 , 88 ]. In carrying out these experiments we became aware of some of the variables involved:…”

Section: Discussionmentioning

confidence: 99%

Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture

Othman,

Zeef,

Szestak

et al. 2023

PLoS ONE

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The human malaria parasite Plasmodium falciparum is responsible for the majority of mortality and morbidity caused by malaria infection and differs from other human malaria species in the degree of accumulation of parasite-infected red blood cells in the microvasculature, known as cytoadherence or sequestration. In P. falciparum, cytoadherence is mediated by a protein called PfEMP1 which, due to its exposure to the host immune system, undergoes antigenic variation resulting in the expression of different PfEMP1 variants on the infected erythrocyte membrane. These PfEMP1s contain various combinations of adhesive domains, which allow for the differential engagement of a repertoire of endothelial receptors on the host microvasculature, with specific receptor usage associated with severe disease. We used a co-culture model of cytoadherence incubating human brain microvascular endothelial cells with erythrocytes infected with two parasite lines expressing different PfEMP1s that demonstrate different binding profiles to vascular endothelium. We determined the transcriptional profile of human brain microvascular endothelial cells (HBMEC) following different incubation periods with infected erythrocytes, identifying different transcriptional profiles of pathways previously found to be involved in the pathology of severe malaria, such as inflammation, apoptosis and barrier integrity, induced by the two PfEMP1 variants.

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Developing a xenograft model of human vasculature in the mouse ear pinna

Cited by 7 publications

References 44 publications

An in vivo model allowing continuous observation of human vascular formation in the same animal over time

An in vivo model allowing continuous observation of human vascular formation in the same animal over time

A simple agent-based model to simulate 3D tumor-induced angiogenesis considering the evolution of the hypoxic conditions of the cells

Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture

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