Bone Marrow Origin of Endothelial Progenitor Cells Responsible for Postnatal Vasculogenesis in Physiological and Pathological Neovascularization

• DOI: 10.1161/01.res.85.3.221
• Publication Date: 2012-06-12T00:47:05Z
• Authors: Takayuki Asahara; Haruchika Masuda; Tomono Takahashi; Christoph Kalka; Christopher Pastore; Marcy Silver; Marianne Kearne; Meredith Magner; Jeffrey M. Isner
• Keywords: Vasculogenesis; Megakaryocytopoiesis

Abstract —Circulating endothelial progenitor cells (EPCs) have been isolated in peripheral blood of adult species. To determine the origin and role EPCs contributing to postnatal vasculogenesis, transgenic mice constitutively expressing β-galactosidase under transcriptional regulation an cell–specific promoter (Flk-1/LZ or Tie-2/LZ) were used as transplant donors. Localization EPCs, indicated by flk-1 tie-2/lacZ fusion transcripts, identified corpus luteal endometrial neovasculature after inductive ovulation. Mouse syngeneic colon cancer (MCA38) implanted subcutaneously into Flk-1/LZ/BMT (bone marrow transplantation) Tie-2/LZ/BMT mice; tumor samples harvested at 1 week disclosed abundant flk-1/lacZ sections stained with X-gal demonstrated that developing frequently comprised Flk-1– Tie-2–expressing EPCs. Cutaneous wounds examined 4 days 7 skin removal punch biopsy incorporated foci neovascularization high frequency. One onset hindlimb ischemia, lacZ-positive capillaries among skeletal myocytes. After permanent ligation left anterior descending coronary artery, histological from sites myocardial infarction incorporation border infarct. These findings indicate does not rely exclusively on sprouting preexisting vessels (angiogenesis); instead, circulate bone incorporate thus contribute physiological pathological neovascularization, which is consistent vasculogenesis.