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

Abstract 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,...

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Autores principales:	Yohei Tsukada, Fumitaka Muramatsu, Yumiko Hayashi, Chiaki Inagaki, Hang Su, Tomohiro Iba, Hiroyasu Kidoya, Nobuyuki Takakura
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3dc28d15ce0443be96af6006545bcfeb
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spelling	oai:doaj.org-article:3dc28d15ce0443be96af6006545bcfeb2021-12-02T14:01:33ZAn in vivo model allowing continuous observation of human vascular formation in the same animal over time10.1038/s41598-020-80497-62045-2322https://doaj.org/article/3dc28d15ce0443be96af6006545bcfeb2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80497-6https://doaj.org/toc/2045-2322Abstract 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.Yohei TsukadaFumitaka MuramatsuYumiko HayashiChiaki InagakiHang SuTomohiro IbaHiroyasu KidoyaNobuyuki TakakuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yohei Tsukada Fumitaka Muramatsu Yumiko Hayashi Chiaki Inagaki Hang Su Tomohiro Iba Hiroyasu Kidoya Nobuyuki Takakura An in vivo model allowing continuous observation of human vascular formation in the same animal over time
description	Abstract 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.
format	article
author	Yohei Tsukada Fumitaka Muramatsu Yumiko Hayashi Chiaki Inagaki Hang Su Tomohiro Iba Hiroyasu Kidoya Nobuyuki Takakura
author_facet	Yohei Tsukada Fumitaka Muramatsu Yumiko Hayashi Chiaki Inagaki Hang Su Tomohiro Iba Hiroyasu Kidoya Nobuyuki Takakura
author_sort	Yohei Tsukada
title	An in vivo model allowing continuous observation of human vascular formation in the same animal over time
title_short	An in vivo model allowing continuous observation of human vascular formation in the same animal over time
title_full	An in vivo model allowing continuous observation of human vascular formation in the same animal over time
title_fullStr	An in vivo model allowing continuous observation of human vascular formation in the same animal over time
title_full_unstemmed	An in vivo model allowing continuous observation of human vascular formation in the same animal over time
title_sort	in vivo model allowing continuous observation of human vascular formation in the same animal over time
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3dc28d15ce0443be96af6006545bcfeb
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An in vivo model allowing continuous observation of human vascular formation in the same animal over time

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