Low-energy shock wave for enhancing recruitment of endothelial progenitor cells - A new modality to increase efficacy of cell therapy in chronic hind limb ischemia
Low-energy shock wave for enhancing recruitment of endothelial progenitor cells - A new modality to increase efficacy of cell therapy in chronic hind limb ischemia
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DOI：
10.1161/circulationaha.106.628623
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发表时间：
2006-12-19
期刊：
影响因子：
37.8
通讯作者：
Dimmeler, Stefanie
中科院分区：
文献类型：
--
作者：
Aicher, Alexandra;Heeschen, Christopher;Dimmeler, Stefanie
背景-干细胞和祖细胞治疗是改善缺血组织新生血管和功能的一种新方法。化学引诱因子如基质细胞衍生因子1和血管内皮生长因子的增强的组织表达对于急性缺血期间循环内皮祖细胞（EPCs）的募集是至关重要的。然而，在慢性缺血中，这些趋化因子的表达不太明显，这导致EPC募集到靶组织中的不足。因此，我们研究了有针对性的体外冲击波（SW）的应用，以促进EPC招聘到非缺血性和慢性缺血tissue.Methods和结果-后肢内收肌的裸大鼠进行了治疗与500，1000，2000脉冲的集中低能量SW（通量密度水平：0.05 mJ/mm（2））。24小时后，化学引诱物基质细胞衍生因子1的mRNA表达在1000次脉冲（基质细胞衍生因子1/GAPDH：0.95 +/-0.09）和2000次脉冲（基质细胞衍生因子1/GAPDH：1.17 +/-0.24;与未处理相比均P < 0.05）下显著增加。在组织学上，2000次脉冲时，每个肌细胞中血管内皮生长因子阳性内皮细胞的数量显著增加（0.24 +/- 0.05对0.09 +/- 0.02; P < 0.01）。这种预处理作用导致SW处理后24小时静脉输注的EPCs的募集和归巢显着增强（P < 0.05）。在慢性后肢缺血的大鼠模型中，SW促进的EPC治疗导致相对血流恢复的显著增加，如通过激光多普勒成像评估的（P < 0.05）。结论：用低能量SW预处理非缺血和慢性缺血组织，通过增强趋化因子的表达，改善循环EPCs的募集。因此，SW促进的细胞疗法可能会提高EPC治疗慢性缺血患者的疗效。
Background - Stem and progenitor cell therapy is a novel approach to improve neovascularization and function of ischemic tissue. Enhanced tissue expression of chemoattractant factors such as stromal cell - derived factor 1 and vascular endothelial growth factor is crucial for the recruitment of circulating endothelial progenitor cells (EPCs) during acute ischemia. In chronic ischemia, however, expression of these chemoattractants is less pronounced, which results in insufficient EPC recruitment into the target tissue. Therefore, we investigated the effect of targeted extracorporeal shock wave (SW) application in order to facilitate EPC recruitment into nonischemic and chronic ischemic tissue.Methods and Results - Hind limb adductor muscles of nude rats were treated with 500, 1000, and 2000 impulses of focused low-energy SW (flux density level: 0.05 mJ/mm(2)). Twenty-four hours later, mRNA expression of the chemoattractant stromal cell - derived factor 1 was significantly increased with 1000 impulses (stromal cell derived factor 1/GAPDH: 0.95 +/- 0.09) and 2000 impulses (stromal cell-derived factor 1/GAPDH: 1.17 +/- 0.24; both P < 0.05 versus untreated). Histologically, the number of vascular endothelial growth factor-positive endothelial cells per myocyte was significantly increased with 2000 impulses (0.24 +/- 0.05 versus 0.09 +/- 0.02; P < 0.01). This preconditioning effect resulted in significantly enhanced recruitment and homing of EPCs that were intravenously infused 24 hours after SW treatment (P < 0.05). In a rat model of chronic hind limb ischemia, SW-facilitated EPC treatment resulted in a significant increase in relative blood flow recovery as assessed by laser Doppler imaging (P < 0.05).Conclusions - Preconditioning of both nonischemic and chronic ischemic tissue with low-energy SW improves recruitment of circulating EPCs via enhanced expression of chemoattractant factors. Thus, SW-facilitated cell therapy may improve the efficacy of EPC treatment in patients with chronic ischemia.