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Originally published online as doi:10.2353/ajpath.2008.070840 on February 14, 2008

Published online before print February 14, 2008
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(American Journal of Pathology. 2008;172:839-848.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.070840

Long-Term Engraftment of Bone Marrow-Derived Cells in the Intimal Hyperplasia Lesion of Autologous Vein Grafts

Yanpeng Diao*§, Steve Guthrie{dagger}, Shen-Ling Xia*||, Xiaosen Ouyang*, Li Zhang*, Jing Xue{ddagger}, Pui Lee*, Maria Grant{dagger}, Edward Scott{dagger} and Mark S. Segal*

Division of Nephrology, Hypertension and Transplantation,*Program in Stem Cell Biology,{dagger}Department of Orthodontics,{ddagger}University of Florida, Gainesville; North Florida/South Georgia Veterans Health System,||Gainesville, Florida; Division of Vascular Surgery,§The 1st Teaching Hospital, China Medical University, Shenyang; and Department of Surgery,The 1st Teaching Hospital, Dalian Medical University, Dalian, China

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.






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Copyright © 2008 by the American Society for Investigative Pathology.