Vascular-Resident Endothelial Side Population Cells

  • Hisamichi NaitoEmail author
  • Nobuyuki Takakura


Postnatal neovascular formation was originally thought to be mediated by angiogenesis, which is defined as the formation of new blood vessels from pre-existing endothelial cells (ECs). However, over the last decade, it has been proposed that vasculogenesis, that is, de novo blood vessel generation from endothelial progenitor cells (EPCs) derived from bone marrow, may persist into adult life. Nonetheless, it is still a matter of debate as to what extent the EPCs contribute to new vessel formation in the adult.

In the peripheral blood vessels, the presence of different stem and progenitor cell types residing in the media and adventitia of the vascular wall has been suggested. These stem/progenitor cells were reported to have the ability to differentiate into ECs in culture and form capillary-like microvessels in ex vivo assays. However, the precise roles of these cells during angiogenic growth are not well defined. We recently isolated a novel endothelial stem/progenitor-like cells from the intima of adult murine blood vessels using the Hoechst method in which stem cell populations are identified as side populations. This vascular endothelial side population cell possesses colony-forming ability, generates large numbers of ECs, and when transplanted into ischemic lesions, these cells contribute to the newly formed long-term surviving blood vessels and restore blood flow completely. Our discovery of vascular endothelial side population cells that have features of endothelial stem/progenitor cells may lead to the identification of new targets for vascular regeneration therapy as well as vascular disrupting therapy.


Endothelium Side population FACS analysis Heterogeneity Stemness Regeneration 



Bone marrow


Endothelial cells


Endothelial progenitor cells


Fluorescence-activated cell sorting


Human aortic endothelial cells


Hematopoietic cell


Hematopoietic stem cell


Human umbilical vein endothelial cells


c-Kit+ Sca-1+, and Lineage


Main population


Smooth muscle cells


Side population



This work was partially supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology and Japan Society for the Promotion of Science of Japan.


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Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  1. 1.Department of Signal Transduction, Research Institute for Microbial DiseasesOsaka UniversitySuitaJapan
  2. 2.JST, CRESTTokyoJapan

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