Differential activity of bone marrow hematopoietic stem cell subpopulations for EPC development and ischemic neovascularization

Sang Mo Kwon, Yun Kyung Lee, Ayumi Yokoyama, Seok Yun Jung, Haruchika Masuda, Atsuhiko Kawamoto, You Mie Lee, Takayuki Asahara

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Although endothelial progenitor cells (EPCs) differentiate from minor populations of stem cells in bone marrow (BM), the differential role of hematopoietic stem cell (HSC) subpopulations in EPC development is largely unclear. Morphological characterization of EPC colonies has revealed that c-kit+/Sca-1+/lineage (Lin)-(KSL) cells mainly develop small EPC-colony forming units (CFUs) not large EPC-CFUs. In contrast, c-kit+/Sca-1-/Lin- (KL) cells develop large EPC-CFUs not small EPC-CFUs. Neither c-kit-/Sca-1+/Lin- (SL) cells nor c-kit-/Sca-1-/Lin- (L) cells develop EPC-CFUs to an appreciable extent. Hindlimb ischemia enhances formation of large EPC-CFUs from all HSC subpopulations, suggesting an important role for ischemia in functional EPC development. Real time RT-PCR analysis shows that KSL, KL and SL cells but not L cells express various factors at high levels, maintaining a BM-EPC pool. In hindlimb ischemia, transplanted KSL, KL and SL cells efficiently differentiate into endothelial lineage cells in situ and augment capillary density. The percentage of Ki-67+ cycling cells among transplanted cells in ischemic tissue was also greater for KSL, KL and SL cells than L cells. Moreover, the frequency of VEGF- or SDF-1-expressing cells was higher transplanted KSL, KL or SL cells than L cells. Thus, KSL, KL and SL cells are not different in their angiogenic competence under ischemic conditions. In conclusion, although KSL cells are clearly the most potent contributors to EPC development, KL and SL cells may also contribute to neovascularization via both autocrine and paracrine mechanisms in response to ischemic signals.

Original languageEnglish
Pages (from-to)308-317
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume51
Issue number3
DOIs
StatePublished - Sep 2011

Keywords

  • Adult stem cells
  • Angiogenesis
  • C-kit
  • Endothelial progenitor cells
  • Hematopoietic stem cell subpopulations
  • Sca-1
  • Vascular repair

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