Neointimal Formation by Circulating Bone Marrow Cells

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Abstract
The origin of smooth muscle cells involved in vascular healing was examined. Eighteen C57BL/6 (Ly 5.2) female mice underwent whole body irradiation followed by transfusion with 106 bone nucleated marrow cells from congenic (Ly 5.1) male donors. Successful repopulation by donor marrow was demonstrated after 4 weeks by flow cytometry with FITC‐conjugated A20.1/Ly 5.1 monoclonal antibody. The iliac artery of six of the chimeric mice was scratch‐injured by five passes of a probe, causing severe medial damage. After 4 weeks the arterial lumen was obliterated by a cell‐rich neointima, with α‐smooth muscle actin‐containing cells present around the residual lumen. Approximately half of these cells were of male donor origin, as evidenced by in situ hybridization with a Y chromosome‐specific probe. An organized arterial thrombus was formed in the remaining 12 chimeric mice by inserting an 8‐0 silk suture into the left common carotid artery. Donor cells staining with α‐smooth muscle actin were found in those arteries sustaining serious damage but not in arteries with minimal damage. Our results suggest that bone marrow‐derived cells are recruited in vascular healing as a complementary source of smooth muscle‐like cells when the media is severely damaged and few resident smooth muscle cells are available to effect repair.