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Taku Wakabayashi, Hisamichi Naito, Nobuyuki Takakura, Kohji Nishida; Identification of resident vasculoreparative endothelial stem cells responsible for ocular angiogenesis. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5491. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Ocular neovascular diseases, including diabetic retinopathy and the neovascular form of age-related macular degeneration (AMD) are the most common cause of severe vision loss worldwide. Since both retinal and choroidal neovascularization are caused by angiogenesis, further investigation of the mechanism of angiogenesis is warranted. The purpose of the present study is to newly identify the specific vascular endothelial cells (ECs) within the preexisting blood vessels which may play a central role in the initiation and development of angiogenesis.
We created the mice expressing GFP in the control of VEcadherin promoter by mating VEcadherin-Cre mouse and GFP reporter mouse carrying loxP sites. Mice organs (choroid, retina, brain, liver, lung, heart) were freshly isolated and single cell suspensions were prepared by enzymatic digestion. The specific vascular endothelial stem-like population was identified as side population (SP) cells by flow cytometric analysis based on the ability to efflux the DNA-binding dye, Hoechst 33342, via ATP-binding cassette (ABC) transporters.
In the choroid, 2.8% of GFP (VEcadherin) positive vascular ECs showed a typical SP staining pattern. They were not bone marrow-derived and possessed properties of endothelial colony-forming cells (ECFC) in vitro. They proliferated and produced large number of ECs in vivo during laser-induced choroidal neovascularization. Microarray analysis revealed that vascular endothelial SP cells specifically express gene X and establish a hierarchy of vascular endothelial cells. The gene X positive vascular endothelial SP cells were located in the large vessels in the choroid, retina, brain, liver, lung, and heart.
The vascular endothelial SP cells represent vessel-residing endothelial stem cells contributing to angiogenesis, and may be useful for augmenting vascular regeneration or for developing new anti-angiogenic therapy.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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