Bone Marrow Monocyte Lineage Cells Adhere on Injured Endothelium in a Monocyte Chemoattractant Protein-1-Dependent Manner and Accelerate Reendothelialization as Endothelial Progenitor Cells

Soichiro Fujiyama, Katsuya Amano, Kazutaka Uehira, Masayuki Yoshida, Yasunobu Nishiwaki, Yoshihisa Nozawa, Denan Jin, Shinji Takai, Mizuo Miyazaki, Kensuke Egashira, Takayuki Imada, Toshiji Iwasaka, Hiroaki Matsubara

研究成果: ジャーナルへの寄稿学術誌査読

330 被引用数 (Scopus)

抄録

Peripheral blood (PB)-derived CD14+ monocytes were shown to transdifferentiate into endothelial cell (EC) lineage cells and contribute to neovascularization. We investigated whether bone marrow (BM)- or PB-derived CD34-/CD14+ cells are involved in reendothelialization after carotid balloon injury. Although neither hematopoietic nor mesenchymal stem cells were included in human BM-derived CD34-/CD14+ monocyte lineage cells (BM-MLCs), they expressed EC-specific markers (Tie2, CD31, VE-cadherin, and endoglin) to an extent identical to mature ECs. When BM-MLCs were cultured with vascular endothelial growth factors, hematopoietic markers were drastically decreased and new EC-specific markers (Flk and CD34) were induced. BM-MLCs were intra-arterially transplanted into balloon-injured arteries of athymic nude rats. When BM-MLCs were activated by monocyte chemoattractant protein-1 (MCP-1) in vivo or in vitro, they adhered onto injured endothelium, differentiated into EC-like cells by losing hematopoietic markers, and inhibited neointimal hyperplasia. Ability to prevent neointimal hyperplasia was more efficient than that of BM-derived CD34+ cells. MCP-dependent adhesion was not observed in PB-derived CD34-/ CD14+ monocytes. Regenerated endothelium exhibited a cobblestone appearance, blocked extravasation of dye, and induced NO-dependent vasorelaxation. Basal adhesive activities on HUVECs under laminar flow and β1-integrin expression (basal and active forms) were significantly increased in BM-MLCs compared with PB-derived monocytes. MCP-1 markedly enhanced adhesive activity of BM-MLCs (2.8-fold) on HUVECs by activating β1-integrin conformation. Thus, BM-MLCs can function as EC progenitors that are more potent than CD34+ cells and acquire the ability to adhere on injured endothelium in a MCP-1-dependent manner, leading to reendothelialization associated with inhibition of intimal hyperplasia. This will open a novel window to MCP-1-mediated biological actions and vascular regeneration strategies by cell therapy.

本文言語英語
ページ(範囲)980-989
ページ数10
ジャーナルCirculation research
93
10
DOI
出版ステータス出版済み - 11月 14 2003
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 生理学
  • 循環器および心血管医学

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