Mobilized endothelial progenitor cells by granulocyte-macrophage colony-stimulating factor accelerate reendothelialization and reduce vascular inflammation after intravascular radiation.
BACKGROUND
Endothelial progenitor cells (EPCs) play a pivotal role in repair and regeneration of damaged vessels. We investigated the role of mobilized EPCs in the healing process after intravascular radiation therapy.


RESULTS
One iliac artery of hypercholesterolemic rabbits was subjected to balloon injury and intravascular radiation with a Re-188 balloon and the contralateral iliac artery to balloon injury only. Rabbits received granulocyte-macrophage colony-stimulating factor (recombinant human GM-CSF) (60 microg/d subcutaneously) daily for 1 week, either 7 days before the angioplasty or at the time of angioplasty. Control rabbits received human albumin. GM-CSF significantly increased the double-positive (CD31+ and KDR+) fraction in peripheral blood monocytes and showed a higher number of EPCs than albumin after culture and, furthermore, enhanced migration and incorporation of EPCs. In the albumin group, intravascular radiation therapy reduced neointimal hyperplasia but delayed reendothelialization and aggravated monocyte infiltration. GM-CSF treatment significantly accelerated the reendothelialization and inhibited monocyte infiltration (reendothelialization index, 81+/-13% in the GM-CSF radiation [n=7] versus 30+/-11% in the control radiation [n=9] at 2 weeks, P<0.01). GM-CSF treatment produced an additional significant reduction in neointimal formation at 14 and 28 days after injury in the intravascular radiation groups (intima to media ratio, 0.14+/-0.11 in the GM-CSF radiation [n=5] versus 0.36+/-0.07 in the control radiation [n=5] at 4 weeks, P<0.01).


CONCLUSIONS
GM-CSF treatment mobilizes EPCs, accelerates reendothelialization, and reduces monocytes infiltration after intravascular radiation therapy, suggesting that stem cell mobilization is a promising strategy for enhancing the vascular healing process after cytotoxic angioplasty.
Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110-744, Korea.
Hyun-Jai
HJ
Cho
Hyo-Soo
HS
Kim
Myoung-Mook
MM
Lee
Dae-Hee
DH
Kim
Hyun-Ju
HJ
Yang
Jin
J
Hur
Kyoung-Kook
KK
Hwang
Seil
S
Oh
Young-Jin
YJ
Choi
In-Ho
IH
Chae
Byung-Hee
BH
Oh
Yun-Shik
YS
Choi
Kenneth
K
Walsh
Young-Bae
YB
Park
D000818:Animals; D002404:Catheterization / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000293:injuries / Q000473:pathology / Q000502:physiology*; D005487:Foam Cells / Q000528:radiation effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D006937:Hypercholesterolemia / Q000473:pathology; D006965:Hyperplasia; D007083:Iliac Artery / Q000293:injuries* / Q000528:radiation effects; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D011817:Rabbits; D011832:Radiation Injuries / Q000628:therapy*; D011868:Radioisotopes / Q000009:adverse effects; D011994:Recombinant Proteins / Q000494:pharmacology; D012038:Regeneration / Q000528:radiation effects; D012211:Rhenium / Q000009:adverse effects; D017539:Tunica Intima / Q000473:pathology / Q000528:radiation effects; D014945:Wound Healing
D011868:Radioisotopes; D011994:Recombinant Proteins; D012211:Rhenium; D016178:Granulocyte-Macrophage Colony-Stimulating Factor