Department of Respiratory Medicine, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853, PR China.
Int Immunopharmacol. 2011 Oct;11(10):1584-90. doi: 10.1016/j.intimp.2011.05.019. Epub 2011 May 31.
Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are leading causes of morbidity and mortality in critically ill patients. Recent studies suggest that endothelial progenitor cells (EPCs) transplantation could become a novel cell-based therapeutic strategy for ALI/ARDS, but the exact therapeutic effect and possible mechanisms still need to be elucidated. In the present study, autologous circulating EPCs were obtained from rabbits using Ficoll centrifugation and cultured in vitro for 7 days. ALI was induced in rabbits by lipopolysaccharide (LPS), and EPCs were administered systemically. Fluorescence microscopy showed that CM-DiI labelled EPCs could migrate to the injured lung tissues. Reduced pulmonary edema level, inflammation, hemorrhage and hyaline membrane formation were present in rabbit treated with EPCs. EPCs autotransplantation significantly decreased the expression of adhesion molecules of sICAM-1 and P-selectin. Furthermore, EPCs administration mediated a down-regulation of proinflammatory responses (reducing IL-1β and TNF-α) while increasing the anti-inflammatory cytokine IL-10. Apoptosis of endothelial and epithelial cells was substantially reduced in EPCs-treated rabbit. Those findings suggest that autotransplantation of circulating EPCs can reduce the severity of LPS-induced ALI. Possible mechanisms include EPCs engraftment and reendothelization, down-regulation of adhesion molecules, alleviation of inflammatory response and apoptosis prevention.
急性肺损伤和急性呼吸窘迫综合征（ALI/ARDS）是危重病患者发病率和死亡率的主要原因。最近的研究表明，内皮祖细胞（EPCs）移植可能成为 ALI/ARDS 的一种新的细胞治疗策略，但确切的治疗效果和可能的机制仍需要阐明。在本研究中，使用 Ficoll 离心法从兔中获得自体循环 EPCs，并在体外培养 7 天。通过脂多糖（LPS）诱导兔发生 ALI，并进行 EPC 系统给药。荧光显微镜显示 CM-DiI 标记的 EPCs 可迁移至受损的肺组织。用 EPCs 处理的兔肺部水肿程度降低，炎症、出血和透明膜形成减少。EPCs 自体移植显著降低了 sICAM-1 和 P-选择素的粘附分子的表达。此外，EPCs 给药还介导了促炎反应的下调（减少 IL-1β 和 TNF-α），同时增加抗炎细胞因子 IL-10。EPCs 治疗的兔内皮和上皮细胞凋亡明显减少。这些发现表明，循环 EPCs 的自体移植可以减轻 LPS 诱导的 ALI 的严重程度。可能的机制包括 EPCs 移植和再内皮化、粘附分子的下调、炎症反应的缓解和凋亡的预防。
