Identification of functional endothelial progenitor cells suitable for the treatment of ischemic tissue using human umbilical cord blood

Masumi Nagano, Toshiharu Yamashita, Hiromi Hamada, Kinuko Ohneda, Ken Ichi Kimura, Tomoki Nakagawa, Masabumi Shibuya, Hiroyuki Yoshikawa, Osamu Ohneda

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)

Abstract

Umbilical cord blood (UCB) has been used as a potential source of various kinds of stem cells, including hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells (EPCs), for a variety of cell therapies. Recently, EPCs were introduced for restoring vascularization in ischemic tissues. An appropriate procedure for isolating EPCs from UCB is a key issue for improving therapeutic efficacy and eliminating the unexpected expansion of nonessential cells. Here we report a novel method for isolating EPCs from UCB by a combination of negative immunoselection and cell culture techniques. In addition, we divided EPCs into 2 subpopulations according to the aldehyde dehydrogenase (ALDH) activity. We found that EPCs with low ALDH activity (Alde-Low) possess a greater ability to proliferate and migrate compared to those with high ALDH activity (Alde-High). Moreover, hypoxia-inducible factor proteins are up-regulated and VEGF, CXCR4, and GLUT-1 mRNAs are increased in Alde-Low EPCs under hypoxic conditions, while the response was not significant in Alde-High EPCs. In fact, the introduction of Alde-Low EPCs significantly reduced tissue damage in ischemia in a mouse flap model. Thus, the introduction of Alde-Low EPCs may be a potential strategy for inducing rapid neovascularization and subsequent regeneration of ischemic tissues.

Original languageEnglish
Pages (from-to)151-160
Number of pages10
JournalBlood
Volume110
Issue number1
DOIs
Publication statusPublished - 2007 Jul 1
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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