中文題目：血管內直接移植c-kit表現強化之內皮幹細胞可改善血管整形術後的
血管再狹窄
英文題目：Direct intravascular transplantation with c-kit-overexpressing late
endothelial progenitor cells attenuates intimal hyperplasia after angioplasty
作
者：王兆弘1. 2 梅秀富1 程文俊1. 2 郭李堂1 楊甯貽1
服務單位：財團法人基隆長庚紀念醫院心臟內科1 長庚大學2
Background: Expression of stem cell factor (SCF) on vessel wall is upregulated after
vascular injury. C-kit, the receptor of SCF, is a marker of endothelial progenitor cell
(EPC) and probably links to the homing of EPCs to the injured vasculature. This
study sought to investigate whether c-kit-overexpressing late EPCs, so-called late
outgrowth endothelial cell (OEC), help early re-endothelialization and attenuate
intimal hyperplasia after vascular injury.
Methods and Results: In vitro and in vivo cell adhesion assays were performed.
Mouse femoral artery wire-injury model was used to investigate the effect of cell
therapy on intimal hyperplasia after vascular injury. For in vitro study, mouse bone
marrow c-kit+ cells were used to test the function of c-kit receptor. After SCF
stimulation, the adhesion capacity of c-kit+ cells significantly increased (increased
3-fold compared to the controls, p<0.01). In vivo, c-kit+ cells had a 5-fold increase in
adhesive capacity to injured vessel wall, compared to c-kit- cells (p<0.0001). C-kit+
cells differentiated to endothelial cells after adherence to injured vessel wall and
attenuated the amount of intimal hyperplasia one month after vascular injury,
compared to the controls (I/M ratio from 4.12.2 to 2.51.2, p<0.001). Then, human
OECs were gene-manipulated to overexpress c-kit receptor. In the meanwhile, OECs
were also transfected with double reporter genes expressing eGFP and luciferase for
cell tracking both by living animal system and fluorescence immunostaining.
Compared to OECs before transfection, the c-kit expression rate of OECs
significantly increased after transfection (from 3.2%1.1% to 89.5%7.2%, p<0.001).
Transplantaion of OECs to nude mice after vascular injury significantly attenuated the
amount of intimal hyperplasia.
Conclusions: Cell therapy with c-kit-overexpressing peripheral blood-derived late
outgrowth endothelial cells attenuates intimal hyperplasia after vascular injury.
However, long-term results and adverse effects need to be further monitored.