title: Autologous Bone Marrow Mononuclear Cell Transplantation Delays Progression of Carotid Atherosclerosis in Rabbits.
abstract: Bone marrow mononuclear cells (BMMNCs) can counteract oxidative stress and inhibit the inflammatory response in focal ischemic stroke models. However, the effect of BMMNC transplantation on carotid atherosclerosis needs to be determined. The carotid atherosclerotic plaque model was established in New Zealand White rabbits by balloon injury and 8 weeks of high-fat diet. Rabbits were randomized to receive an intravenous injection of autologous bromodeoxyuridine (BrdU)-labeled BMMNCs or an equal volume of phosphate-buffered saline. Plaques were evaluated for expression of proinflammatory and anti-inflammatory cytokines, anti-oxidant proteins, and markers of cell death. BMMNCs migrated into atherosclerotic plaque on the first day after cell transplantation. BMMNC-treated rabbits had smaller plaques and more collagen deposition than did the vehicle-treated controls on day 28 (p < 0.05). BMMNC treatment significantly increased endothelial nitric oxide synthase and the anti-oxidant enzymes glutathione peroxidase and superoxide dismutase in plaques compared to vehicle treatment on day 7. BMMNC-treated rabbits also had lower levels of cleaved caspase-3 expression; lower levels of proinflammatory cytokines interleukin-1β, tumor necrosis factor alpha, and matrix metalloproteinase 9; and higher levels of insulin-like growth factor-1 and its receptor (p < 0.05). Autologous BMMNC transplantation can suppress the process of atherosclerotic plaque formation and is associated with enhanced anti-oxidative effect, reduced levels of inflammatory cytokines and cleaved caspase-3, and increased expression of insulin-like growth factor-1 and its receptor. BMMNC transplantation represents a novel approach for the treatment of carotid atherosclerosis.
authors.affiliation: Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. cuikefei2010@126.com.
authors.forename: Kefei
authors.initials: K
authors.lastname: Cui
authors.affiliation: Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
authors.forename: Lie
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.|Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Fu
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
authors.forename: Yuanjing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
authors.forename: Suyun
authors.initials: S
authors.lastname: Hou
authors.affiliation: Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
authors.forename: Caifeng
authors.initials: C
authors.lastname: Si
authors.affiliation: Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
authors.forename: Zhengguang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: Jieru
authors.initials: J
authors.lastname: Wan
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA. jwang79@jhmi.edu.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy*; D002465:Cell Movement; D004195:Disease Models, Animal; D018450:Disease Progression; D007249:Inflammation / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D018384:Oxidative Stress; D058226:Plaque, Atherosclerotic / Q000473:pathology; D011817:Rabbits; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction; D014182:Transplantation, Autologous; D015854:Up-Regulation
chemical_list: D008055:Lipids; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
keywords: Atherosclerosis; Bone marrow mononuclear cell; Inflammatory; Insulin-like growth factor; Oxidative stress