Aging impairs the mobilization and homing of bone marrow-derived angiogenic cells to burn wounds.
Aging impairs the mobilization and homing of bone marrow-derived angiogenic cells to burn wounds.
复制标题
衰老会损害骨髓来源的血管生成细胞对烧伤伤口的动员和归巢。
DOI：
10.1007/s00109-011-0754-2
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Harmon,JohnW
中科院分区：
文献类型：
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作者：
Zhang,Xianjie;Sarkar,Kakali;Rey,Sergio;Sebastian,Raul;Andrikopoulou,Efstathia;Marti,GuyP;Fox-Talbot,Karen;Semenza,GreggL;Harmon,JohnW
老年人的伤口愈合受损是一个主要的临床问题。描述衰老损害伤口愈合的细胞和分子机制可能会导致针对伤口不愈合的老年患者开发改进的治疗策略。新血管形成是伤口愈合的重要步骤，骨髓源性血管生成细胞（BMDAC）在血管形成中发挥着重要作用。使用小鼠全层烧伤创面模型，我们证明烧伤创面的灌注和血管化因衰老而受损，并且与带有细胞表面分子 CXCR4 和 Sca1 的 BMDAC 的动员显着减少有关。基质衍生因子 1 (SDF-1)（CXCR4 的细胞因子配体）的表达在老年小鼠的外周血和烧伤创面中显着降低。在年轻（2 个月大）小鼠的烧伤创面中检测到缺氧诱导因子（HIF）-1α 的表达，但在老年（2 岁）小鼠的烧伤创面中未检测到。当静脉注射来自年轻供体小鼠的 BMDAC 时，年老受体小鼠烧伤伤口组织的归巢受到损害，而 BMDAC 供体小鼠的年龄对归巢没有影响。我们的研究结果表明，由于 HIF-1 诱导和 SDF-1 信号转导受损，衰老会损害 BMDAC 的动员及其向烧伤创面组织的归巢，从而损害烧伤创面血管化。
Impaired wound healing in the elderly represents a major clinical problem. Delineating the cellular and molecular mechanisms by which aging impairs wound healing may lead to the development of improved treatment strategies for elderly patients with non-healing wounds. Neovascularization is an essential step in wound healing, and bone marrow-derived angiogenic cells (BMDACs) play an important role in vascularization. Using a mouse full-thickness burn wound model, we demonstrate that perfusion and vascularization of burn wounds were impaired by aging and were associated with dramatically reduced mobilization of BMDACs bearing the cell surface molecules CXCR4 and Sca1. Expression of stromal-derived factor 1 (SDF-1), the cytokine ligand for CXCR4, was significantly decreased in peripheral blood and burn wounds of old mice. Expression of hypoxia-inducible factor (HIF)-1α was detected in burn wounds from young (2-month-old), but not old (2-year-old), mice. When BMDACs from young donor mice were injected intravenously, homing to burn wound tissue was impaired in old recipient mice, whereas the age of the BMDAC donor mice had no effect on homing. Our results indicate that aging impairs burn wound vascularization by impairing the mobilization of BMDACs and their homing to burn wound tissue as a result of impaired HIF-1 induction and SDF-1 signaling.