Effects of Intratracheal Mesenchymal Stromal Cell Therapy during Recovery and Resolution after Ventilator-induced Lung Injury
Effects of Intratracheal Mesenchymal Stromal Cell Therapy during Recovery and Resolution after Ventilator-induced Lung Injury
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DOI：
10.1097/aln.0b013e318287ba08
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发表时间：
2013-04-01
期刊：
影响因子：
8.8
通讯作者：
Laffey, John G.
中科院分区：
文献类型：
--
作者：
Curley, Gerard F.;Ansari, Bilal;Laffey, John G.
背景资料：间充质基质细胞（MSC）已被证明可以减轻急性肺损伤时，通过静脉或肺内途径交付。作者旨在确定静脉内MSC治疗的有效性和作用机制，并比较其在促进通气诱导的肺损伤后肺修复方面的有效性与静脉内MSC therapy.Methods：麻醉诱导后，大鼠经口气管插管并进行通气诱导的肺损伤（呼吸频率18 min（-1），P-insp 35 cm H2O），以产生严重的肺损伤。恢复后，将动物随机接受：（1）无治疗，n = 4;（2）肠内给药（磷酸盐缓冲液，300 μ l，n = 8）;（3）气管内成纤维细胞（4 × 106个细胞，n = 8）;（4）骨髓间充质干细胞（4 × 106个细胞，n = 8）;（5）气管内条件培养基（300 μ l，n = 8）;或（6）静脉内MSC（4 × 106个细胞，n = 4）。急性肺损伤后的恢复程度和48小时后的炎症反应进行了评估。骨髓间充质干细胞治疗增强了机械通气诱导的肺损伤后的修复，改善了动脉氧合（平均值+/- SD，146 +/- 3.9 vs. 110.8 +/- 21.5 mmHg），恢复肺顺应性（1.04 +/- 0.11 vs. 0.83 +/- 0.06 ml.cm H2O-1），减少肺总水量，并减少肺部炎症和组织学损伤。骨髓间充质干细胞治疗降低了肺泡肿瘤坏死因子-α（130 +/- 43 vs. 488 +/- 211 pg.ml（-1））和白细胞介素-6浓度（138 +/- 18 vs. 260 +/- 82 pg.ml（-1））。骨髓间充质干细胞的疗效与静脉内MSC治疗相当。intraperitheal间充质干细胞似乎通过旁分泌机制，与条件MSC培养基也增强肺修复后injure.Conclusions：intraperitheal间充质干细胞治疗增强恢复后，通过旁分泌机制的通气诱导的肺损伤，是有效的静脉MSC治疗。
Background: Mesenchymal stromal cells (MSCs) have been demonstrated to attenuate acute lung injury when delivered by intravenous or intratracheal routes. The authors aimed to determine the efficacy of and mechanism of action of intratracheal MSC therapy and to compare their efficacy in enhancing lung repair after ventilation-induced lung injury with intravenous MSC therapy.Methods: After induction of anesthesia, rats were orotracheally intubated and subjected to ventilation-induced lung injury (respiratory rate 18 min(-1), P-insp 35 cm H2O,) to produce severe lung injury. After recovery, animals were randomized to receive: (1) no therapy, n = 4; (2) intratracheal vehicle (phosphate-buffered saline, 300 mu l, n = 8); (3) intratracheal fibroblasts (4 x 106 cells, n = 8); (4) intratracheal MSCs (4 x 106 cells, n = 8); (5) intratracheal conditioned medium (300 mu l, n = 8); or (6) intravenous MSCs (4 x 106 cells, n = 4). The extent of recovery after acute lung injury and the inflammatory response was assessed after 48 h.Results: Intratracheal MSC therapy enhanced repair after ventilation-induced lung injury, improving arterial oxygenation (mean +/- SD, 146 +/- 3.9 vs. 110.8 +/- 21.5 mmHg), restoring lung compliance (1.04 +/- 0.11 vs. 0.83 +/- 0.06 ml.cm H2O-1), reducing total lung water, and decreasing lung inflammation and histologic injury compared with control. Intratracheal MSC therapy attenuated alveolar tumor necrosis factor-alpha (130 +/- 43 vs. 488 +/- 211 pg.ml(-1)) and interleukin-6 concentrations (138 +/- 18 vs. 260 +/- 82 pg.ml(-1)). The efficacy of intratracheal MSCs was comparable with intravenous MSC therapy. Intratracheal MSCs seemed to act via a paracine mechanism, with conditioned MSC medium also enhancing lung repair after injury.Conclusions: Intratracheal MSC therapy enhanced recovery after ventilation-induced lung injury via a paracrine mechanism, and was as effective as intravenous MSC therapy.