Bone marrow-derived mononuclear cell therapy in experimental pulmonary and extrapulmonary acute lung injury
Bone marrow-derived mononuclear cell therapy in experimental pulmonary and extrapulmonary acute lung injury
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DOI：
10.1097/ccm.0b013e3181e796d2
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发表时间：
2010-08-01
影响因子：
8.8
通讯作者：
Rocco, Patricia R. M.
中科院分区：
文献类型：
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作者：
Araujo, Indianara M.;Abreu, Soraia C.;Rocco, Patricia R. M.
目的：推测骨髓单个核细胞(BMDMC)对机械损伤相似的肺和肺外急性肺损伤模型的肺和远端器官的作用不同。急性肺损伤的病理生理机制因原发损伤类型不同而不同。设计：前瞻性、随机、对照、实验研究。地点：大学研究实验室。测量和主要结果：对照动物，无菌生理盐水注入气管内(0.05毫升)或腹膜内(0.5毫升)。急性肺损伤动物气管内注射大肠杆菌脂多糖(40 mU g，ALIP)或腹膜内注射(400 mU g，ALIexp)。脂多糖注射6h后，ALIP和ALIexp动物进一步随机分为生理盐水组(0.05mL)和BMDMC组(2×10(6))。第7天，BMDMC组小鼠存活率提高，静态肺弹性、肺泡塌陷、肺泡灌洗液细胞数减少(ALIExp组高于ALIP组)，肺、肾、肝组织胶原纤维含量、细胞凋亡率、肺泡灌洗液中IL-6、KC、IL-10水平下降，胰岛素样生长因子、血小板衍生生长因子、转化生长因子-β信使RNA表达下降，基底膜、上皮、内皮细胞修复，与急性肺损伤无关；4)两种急性肺损伤模型大鼠肺泡灌洗液中血管内皮生长因子水平及肺组织信使RNA表达均增加；5)ALIExp组大鼠肺、肾、肝组织中绿色荧光蛋白阳性细胞数增加。结论：BMDMC治疗对两种急性肺损伤模型的炎症和纤维化过程均有有效的调节作用，但ALIexp组大鼠的存活率、肺力学和组织学改善更明显。这些变化可能归因于旁分泌作用，平衡了促炎和抗炎细胞因子和生长因子，因为观察到少量的肺BMDMC植入。(Crit Care Med 2010；38：1733-1741)
Objective: To hypothesize that bone marrow-derived mononuclear cell (BMDMC) therapy might act differently on lung and distal organs in models of pulmonary or extrapulmonary acute lung injury with similar mechanical compromises. The pathophysiology of acute lung injury differs according to the type of primary insult.Design: Prospective, randomized, controlled, experimental study.Setting: University research laboratory.Measurements and Main Results: In control animals, sterile saline solution was intratracheally (0.05 mL) or intraperitoneally (0.5 mL) injected. Acute lung injury animals received Escherichia coli lipopolysaccharide intratracheally (40 mu g, ALIp) or intraperitoneally (400 mu g, ALIexp). Six hours after lipopolysaccharide administration, ALIp and ALIexp animals were further randomized into subgroups receiving saline (0.05 mL) or BMDMC (2 x 10(6)) intravenously. On day 7, BMDMC led to the following: 1) increase in survival rate; 2) reduction in static lung elastance, alveolar collapse, and bronchoalveolar lavage fluid cellularity (higher in ALIexp than ALIp); 3) decrease in collagen fiber content, cell apoptosis in lung, kidney, and liver, levels of interleukin-6, KC (murine interleukin-8 homolog), and interleukin-10 in bronchoalveolar lavage fluid, and messenger RNA expression of insulin-like growth factor, platelet-derived growth factor, and transforming growth factor-beta in both groups, as well as repair of basement membrane, epithelium and endothelium, regardless of acute lung injury etiology; 4) increase in vascular endothelial growth factor levels in bronchoalveolar lavage fluid and messenger RNA expression in lung tissue in both acute lung injury groups; and 5) increase in number of green fluorescent protein-positive cells in lung, kidney, and liver in ALIexp.Conclusions: BMDMC therapy was effective at modulating the inflammatory and fibrogenic processes in both acute lung injury models; however, survival and lung mechanics and histology improved more in ALIexp. These changes may be attributed to paracrine effects balancing pro-and anti-inflammatory cytokines and growth factors, because a small degree of pulmonary BMDMC engraftment was observed. (Crit Care Med 2010; 38: 1733-1741)