Long-term engraftment of bone marrow-derived cells in the intimal hyperplasia lesion of autologous vein grafts.
Intimal hyperplasia of autologous vein grafts is a critical problem affecting the long-term patency of many types of vascular reconstruction. Within intimal hyperplasia lesions, smooth muscle cells are a major component, playing an essential role in the pathological process. Given that bone marrow-derived cells may differentiate into smooth muscle cells in the neointima of injured arteries, we hypothesized that the bone marrow may serve as a source for some of the smooth muscle cells within intimal hyperplasia lesions of vein grafts. To test this hypothesis, we used an established mouse model for intimal hyperplasia in wild-type mice that had been transplanted with bone marrow from a green fluorescent protein (GFP+/+) transgenic mouse. High-resolution confocal microscopy analysis performed 2 and 8 weeks after grafting demonstrated expression of GFP in 5.4 +/- 0.8% and 11.9 +/- 2.3%, respectively, of smooth muscle cells within intimal hyperplasia lesions. By 16 weeks, GFP expression in smooth muscle cells was not detected by immunohistochemistry; however, real-time PCR revealed that 20.2 +/- 1.7% of the smooth muscle cells captured from the neointima lesion by laser capture microdissection at 16 weeks contained GFP DNA. Our results suggest that bone marrow-derived cells differentiated into smooth muscle cells within the intimal lesion and may provide a novel clinical approach for decreasing intimal hyperplasia in vein grafts.
Diao
Yanpeng
Y
Division of Nephrology, Hypertension and Transplantation, University of Florida, Gainesville, FL, USA.
Guthrie
Steve
S
Xia
Shen-Ling
SL
Ouyang
Xiaosen
X
Zhang
Li
L
Xue
Jing
J
Lee
Pui
P
Grant
Maria
M
Scott
Edward
E
Segal
Mark S
MS
D000818:Animals; D016026:Bone Marrow Transplantation / Q000502:physiology*; D049109:Cell Proliferation; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006965:Hyperplasia / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D042282:Microdissection; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D017539:Tunica Intima / Q000473:pathology*; D014680:Veins / Q000637:transplantation*
D049452:Green Fluorescent Proteins