PMID- 14525810
OWN - NLM
STAT- MEDLINE
DCOM- 20031203
LR  - 20220224
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 93
IP  - 10
DP  - 2003 Nov 14
TI  - Bone marrow monocyte lineage cells adhere on injured endothelium in a monocyte 
      chemoattractant protein-1-dependent manner and accelerate reendothelialization as 
      endothelial progenitor cells.
PG  - 980-9
AB  - 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 beta1-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 
      beta1-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.
FAU - Fujiyama, Soichiro
AU  - Fujiyama S
AD  - Department of Medicine II, Kansai Medical University, Japan.
FAU - Amano, Katsuya
AU  - Amano K
FAU - Uehira, Kazutaka
AU  - Uehira K
FAU - Yoshida, Masayuki
AU  - Yoshida M
FAU - Nishiwaki, Yasunobu
AU  - Nishiwaki Y
FAU - Nozawa, Yoshihisa
AU  - Nozawa Y
FAU - Jin, Denan
AU  - Jin D
FAU - Takai, Shinji
AU  - Takai S
FAU - Miyazaki, Mizuo
AU  - Miyazaki M
FAU - Egashira, Kensuke
AU  - Egashira K
FAU - Imada, Takayuki
AU  - Imada T
FAU - Iwasaka, Toshiji
AU  - Iwasaka T
FAU - Matsubara, Hiroaki
AU  - Matsubara H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20031002
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Chemokine CCL2)
SB  - IM
MH  - Angioplasty, Balloon/adverse effects
MH  - Animals
MH  - Antigens, Differentiation/biosynthesis
MH  - Bone Marrow Cells/*cytology
MH  - Cell Adhesion/drug effects/immunology/physiology
MH  - Cell Differentiation
MH  - Cell Lineage
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism/pharmacology
MH  - Endothelial Cells/*physiology
MH  - Endothelium, Vascular/immunology/injuries/*physiology
MH  - Gene Transfer Techniques
MH  - Humans
MH  - Monocytes/cytology/immunology/*physiology
MH  - Rats
MH  - Rats, Nude
MH  - Stem Cells/cytology/*physiology
EDAT- 2003/10/04 05:00
MHDA- 2003/12/04 05:00
CRDT- 2003/10/04 05:00
PHST- 2003/10/04 05:00 [pubmed]
PHST- 2003/12/04 05:00 [medline]
PHST- 2003/10/04 05:00 [entrez]
AID - 01.RES.0000099245.08637.CE [pii]
AID - 10.1161/01.RES.0000099245.08637.CE [doi]
PST - ppublish
SO  - Circ Res. 2003 Nov 14;93(10):980-9. doi: 10.1161/01.RES.0000099245.08637.CE. Epub 
      2003 Oct 2.