July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Identification of resident vasculoreparative endothelial stem cells responsible for ocular angiogenesis
Author Affiliations & Notes
  • Taku Wakabayashi
    Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan
    Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, Japan
  • Hisamichi Naito
    Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, Japan
  • Nobuyuki Takakura
    Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, Japan
  • Kohji Nishida
    Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan
  • Footnotes
    Commercial Relationships   Taku Wakabayashi, None; Hisamichi Naito, None; Nobuyuki Takakura, None; Kohji Nishida, None
  • Footnotes
    Support  Grants-in-Aid for Young Scientists B (16K20317) from Japan Society for the Promotion of Science (JSPS)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5491. doi:https://doi.org/
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    • Get Citation

      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)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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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