Autologous Bone Marrow Mononuclear Cell Transplantation Delays Progression of Carotid Atherosclerosis in Rabbits

Kefei Cui, Xiao Ma, Lie Yu, Chao Jiang, Chao Fu, Xiaojie Fu, Xiaofang Yu, Yuanjing Huang, Suyun Hou, Caifeng Si, Zhengguang Chen, Jing Yu, Jieru Wan, Jian Wang

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)4387-4396
Number of pages10
JournalMolecular Neurobiology
Volume53
Issue number7
DOIs
StatePublished - Sep 1 2016

Keywords

  • Atherosclerosis
  • Bone marrow mononuclear cell
  • Inflammatory
  • Insulin-like growth factor
  • Oxidative stress

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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