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Angiogenesis by Bone Marrow Cell Transplantation May Contribute |
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Wednesday, 20 August 2003 |
Shaoheng Zhang(a,b), Ping Zhang(a,b), Jingxuan Guo(b), Zhuqing Jia(a,c), Kangtao Ma(c), Yonggang Liu(b), Chunyan Zhou(a,c)*, Linsong Li(a)
a: Stem Cell Research Center, Peking University
b: Department of Cardiology, The Third Hospital of Peking University
c: Department of Biochemistry and Molecular Biology, The School of Basic Medical Sciences, Peking University
Received 13 June 2003; Accepted 20 October 2003;
Received in revised form 15 October 2003
Source: http://www.elsevier.com
Introduction
Despite advances in the treatment of myocardial infarction (MI), congestive heart failure secondary to infarction continues to be a major complication. The cardiomyocytes lost during MI cannot be regenerated, and the extent of the loss is directly related to the reduced cardiac output [1]. Cell therapy has previously been used in the treatment of this disease in which terminally differentiated cells were irreparably damaged [2]. Recently, it was suggested that bone marrow cell transplantation (BMT) might be effective in the treatment ofMI [3]. There is now compelling evidence that BMT reduces infarction area and improves cardiac function via differentiation and angiogenesis in an ischemic heart model in the late phase post-transplantation (.7 days) [4]. However, the mechanism via which BMT improves cardiac function in the early phase post-transplantation (#7 days), generally before cell differentiation, remains largely a matter of speculation. Most researchers have suggested that transplantation of bone marrow cells into ischemic myocardium enhanced collateral perfusion and regional function via supply of angioblasts and angiogenic ligands such as VEGF [5], but others disagree [6]. Thus, there are probably other mechanisms. Heat shock proteins (HSPs) are correlated with enhanced recovery of myocardial contractility after acute MI [7,8]. HSPs can be induced by brief episodes of several stresses including ischemia, heat shock or injury. HSP32 and HSP70, two members of the cytoprotective proteins family, have been shown to protect cells from ischemic injury [9,10]. In this study, we used a rat myocardial ischemia model to investigate the change of cardiac function following acute MI, and attempted to elucidate the role of myocardial protection and angiogenesis on cardiac function after BMT.
Conclusion
The main findings of this study include (1) at the early phase (1–7 days post-transplantation), BMT upregulated the expression of HSP32, HSP70 and VEGF in both transplanted BM-MNCs and recipient endogenous cardiomyocytes, and enhanced cytoprotection and angiogenesis, which may contribute to recovery of infarcted heart function; and (2) at the late phase, the transplanted bone marrow cells might differentiate into both myocardial and vascular endothelial cells that enhance ischemic cardiac function further. Further research would be required for quantitative analysis of changes in VEGF and HSPs after BMT by using Northern blots, Real-time PCR or Western blots. The relationship between upregulation of HSPs and improvement of cardiac function also needs to be clarified.
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Last Updated ( Tuesday, 15 November 2005 )
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