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

Abstract: 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 3days and 4weeks after transplantation. Rabbits were sacrificed 4weeks 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. [Copyright &y& Elsevier]