Gao C, Li Y
Jinshan Hospital, Fudan University, Department of Burn and Plastic Surgery, Shanghai, China.
Transplant Proc. 2007 Jan-Feb;39(1):268-72. doi: 10.1016/j.transproceed.2006.10.020.
Our previous study demonstrated that prolonged cold preservation promoted neointima formation and remodeling but delayed the subsequent arteriosclerosis of rat abdominal aorta grafts. The mechanisms of this phenomenon remain obscure. In this study, we investigated whether stromal cell derived factor-1 (SDF-1) could play a role in recruiting stem cells to repair and remodel the damaged intima of abdominal aorta grafts.
Male Spague-Dawley rats received abdominal aorta grafts from male Wistar rats. Hematoxylin and eosin staining was performed to assess the structure of graft aortas by measuring the neointimal thickness. Immunohistochemical staining detected SDF-1 expression. RT-PCR demonstrated the expression of CXCR4, the only known natural receptor of SDF-1 expression on stem cells.
The neointimal thickness of the SDF-1 antibody-treated group was inconspicuous; a significant relationship existed between the expression of SDF-1 and the neointimal thickness of the grafts. Furthermore, no CXCR4 was detected in normal abdominal aortas, but it was observed in the grafted abdominal aorta.
Prolonged cold ischemia may delay the graft's arteriosclerosis by selectively chemoattracting stem cells to the damaged intima through SDF-1, the presence of which may predict graft arteriosclerosis and the subsequent development of chronic graft dysfunction (CGD). The SDF-1 antibody slowed the endothelial chimerism by blocking this chemoattration. In addition to mycophenolate mofetil and FK 506, SDF-1 antibody might be a new potential effective strategy to decrease the frequency of CGD.
我们之前的研究表明,长时间的冷保存促进了大鼠腹主动脉移植物的新生内膜形成和重塑,但延迟了随后的动脉硬化。这种现象的机制仍不清楚。在本研究中,我们调查了基质细胞衍生因子-1(SDF-1)是否在募集干细胞以修复和重塑腹主动脉移植物受损内膜中发挥作用。
雄性Spague-Dawley大鼠接受来自雄性Wistar大鼠的腹主动脉移植物。进行苏木精和伊红染色,通过测量新生内膜厚度来评估移植物主动脉的结构。免疫组织化学染色检测SDF-1表达。逆转录聚合酶链反应(RT-PCR)证实了CXCR4的表达,CXCR4是干细胞上已知的SDF-1唯一天然受体。
SDF-1抗体处理组的新生内膜厚度不明显;SDF-1表达与移植物新生内膜厚度之间存在显著关系。此外,在正常腹主动脉中未检测到CXCR4,但在移植的腹主动脉中观察到了CXCR4。
长时间的冷缺血可能通过SDF-1将干细胞选择性地化学吸引至受损内膜,从而延迟移植物的动脉硬化,SDF-1的存在可能预示移植物动脉硬化及随后慢性移植物功能障碍(CGD)的发生。SDF-1抗体通过阻断这种化学吸引减缓了内皮嵌合现象。除霉酚酸酯和FK 506外,SDF-1抗体可能是降低CGD发生率的一种新的潜在有效策略。