title: Little evidence for cell fusion between recipient and donor-derived cells.
abstract: Despite recent advances in immunosuppressive therapy, accelerated coronary atherosclerosis remains a major problem in the long-term survival of cardiac transplant recipients. However, the pathogenesis of the transplant-associated atherosclerosis remains largely unknown. Here, we investigated the origin of the vascular cells that contribute to graft vasculopathy. We performed heterotopic heart transplantation using genetically modified mice that express LacZ or green fluorescent protein (GFP) ubiquitously and constitutively. At 4 weeks after transplantation, the graft coronary arteries developed neointimal hyperplasia, expressing several smooth muscle cell markers. Most of the neointimal cells were composed of recipient cells but not graft medial smooth muscle cells. We seldom detected neointimal cells that were positive for both LacZ and GFP. When we transplanted wild-type cardiac allografts into the chimeric mice whose bone marrow cells had been replaced with those of LacZ-mice or GFP-mice, we observed that most of the neointimal cells were derived from the bone marrow. These findings suggest that recipient bone marrow-derived cells contribute to the pathogenesis of graft arteriosclerosis. Spontaneous cell fusion between recipient and donor-derived cells seems to be a rare event, if it occurs at all.
authors.affiliation: Department of Surgery, University of Tokyo, Graduate School of Medicine, Tokyo 113-8655, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Saiura
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
authors.forename: Miwa
authors.initials: M
authors.lastname: Washida
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sugawara
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hirata
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Makuuchi
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000502:physiology; D002459:Cell Fusion; D002465:Cell Movement / Q000502:physiology; D003324:Coronary Artery Disease / Q000209:etiology* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000473:pathology* / Q000503:physiopathology*; D049452:Green Fluorescent Proteins; D016027:Heart Transplantation / Q000009:adverse effects* / Q000502:physiology; D007202:Indicators and Reagents / Q000494:pharmacology; D007763:Lac Operon; D008164:Luminescent Proteins; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000502:physiology
chemical_list: D007202:Indicators and Reagents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins