Allogeneic bone marrow mesenchymal stem cells transplantation for stabilizing and repairing of atherosclerotic ruptured plaque.

INTRODUCTION: There have been no satisfactory therapies on stabilizing and repairing ruptured plagues nowadays, which are the fundamental causes of acute coronary syndrome (ACS) and stroke. The aim of this study was to investigate the therapeutic potential of bone marrow mesenchymal stem cells (MSCs) in stabilizing and repairing ruptured plaques. MATERIALS AND METHODS: 28 male New Zealand rabbits were randomly divided into 2 groups after establishment of atherosclerotic disrupted plaque model by liquid nitrogen frostbite: MSCs transplantation group and control group. MSCs were isolated, cultured in vitro, and labeled with BrdU. BrdU-incorporated MSCs (MSCs transplantation group) or an equal amount of IMDM medium without MSCs (control group) were transplanted into vessels with ruptured plaque. PAI-1, MMP-9 and hs-CRP were determined by ELISA of blood 3 days and 4 weeks after transplantation. Rabbits were sacrificed 4 weeks after transplantation and plaque repair was assessed by HE and Masson's trichrome staining. Transplanted BrdU-positive cells were identified by immunohistochemistry. RESULTS: Four weeks after MSCs transplantation, PAI-1, MMP-9 and hs-CRP were reduced significantly in all experimental animals (p < 0.001). The reduction was more evident in the transplantation group than in the control group (p < 0.01). In addition, the transplantation group showed dramatically higher numbers of newly formed endothelial cells, collagen fibers, and proliferative BrdU-positive cells at plaque areas. CONCLUSION: This study demonstrates that allogeneic MSCs transplantation can stabilize and repair ruptured plaques, which represents a novel approach for ACS and stroke.

Developing a novel rabbit model of atherosclerotic plaque rupture and thrombosis by cold-induced endothelial injury.

BACKGROUND: It is widely believed that atherosclerotic plaque rupture and subsequent thrombosis leads to acute coronary events and stroke. However, study of the mechanism and treatment of human plaque rupture is hampered by lack of a suitable animal model. Our aim was to develop a novel animal model of atherosclerotic plaque rupture to facilitate the study of human plaque disruption and thrombosis. METHODS: 28 healthy male New Zealand white rabbits were randomly divided into two groups: rabbits in group A (n = 12) were only fed a high-fat diet for eight weeks; rabbits in group B (n = 16) underwent cold-induced endothelial injury with liquid nitrogen, then were given a high-fat diet for eight weeks. After completion of the preparatory regimen, triggering of plaque rupture was attempted by local injection of liquid nitrogen in both groups. RESULTS: All rabbits in group B had disrupted plaques or rupture-driven occlusive thrombus formation, but none in group A showed any effects. More importantly, the cold-induced plaques in our model were reminiscent of human atherosclerotic plaques in terms of architecture, cellular composition, growth characteristics, and patterns of lipid accumulation. CONCLUSION: We successfully developed a novel rabbit model of atherosclerotic plaque rupture and thrombosis, which is simple, fast, inexpensive, and reproducible, and has a low mortality and a high yield of triggering. This model will allow us to better understand the mechanism of human plaque rupture and also to develop plaque-stabilizing therapies.