Paracrine Factors of Multipotent Stromal Cells Ameliorate Lung Injury in an Elastase-induced Emphysema Model
Paracrine Factors of Multipotent Stromal Cells Ameliorate Lung Injury in an Elastase-induced Emphysema Model
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DOI：
10.1038/mt.2010.192
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发表时间：
2011-01-01
影响因子：
12.4
通讯作者：
Saijo, Yasuo
中科院分区：
文献类型：
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作者：
Katsha, Ahmed M.;Ohkouchi, Shinya;Saijo, Yasuo
多能基质细胞（MSC）可改善多种类型的肺损伤。 MSC在损伤部位分化为特定细胞被认为是MSC作用的重要过程。然而，尽管 MSC 减少了弹性蛋白酶诱导的肺气肿模型中的破坏，但 MSC 分化相对较少，这表明 MSC 分化为特定细胞并不能充分解释观察到的恢复。间充质干细胞分泌的体液因子也可能在改善肺气肿中发挥重要作用。为了证实这一假设，在气管内 MSC 或磷酸盐缓冲盐水 (PBS) 给药前 14 天，通过气管内注射弹性蛋白酶在 C57BL/6 小鼠的肺部诱导肺气肿。此后，在几个时间点收集肺部并进行评估。我们的结果表明间充质干细胞减少了弹性蛋白酶诱导的肺气肿的破坏。此外，双重免疫荧光染色显示间充质干细胞很少植入并分化为上皮细胞。实时 PCR 显示肝细胞生长因子 (HGF) 和表皮生长因子 (EGF) 水平升高。实时 PCR 和蛋白质印迹显示肺中分泌性白细胞蛋白酶抑制剂 (SLPI) 的产生增强。体外共培养研究证实了体内观察结果。我们的研究结果表明，间充质干细胞衍生的旁分泌因子是保护肺组织免受弹性蛋白酶损伤的主要机制。
Multipotent stromal cells (MSCs) ameliorate several types of lung injury. The differentiation of MSCs into specific cells at the injury site has been considered as the important process in the MSC effect. However, although MSCs reduce destruction in an elastase-induced lung emphysema model, MSC differentiation is relatively rare, suggesting that MSC differentiation into specific cells does not adequately explain the recuperation observed. Humoral factors secreted by MSCs may also play an important role in ameliorating emphysema. To confirm this hypothesis, emphysema was induced in the lungs of C57BL/6 mice by intratracheal elastase injection 14 days before intratracheal MSC or phosphate-buffered saline (PBS) administration. Thereafter, lungs were collected at several time points and evaluated. Our results showed that MSCs reduced the destruction in elastase-induced emphysema. Furthermore, double immunofluorescence staining revealed infrequent MSC engraftment and differentiation into epithelial cells. Real-time PCR showed increased levels of hepatocyte growth factor (HGF) and epidermal growth factor (EGF). Real-time PCR and western blotting showed enhanced production of secretory leukocyte protease inhibitor (SLPI) in the lung. In-vitro coculture studies confirmed the in vivo observations. Our findings suggest that paracrine factors derived from MSCs is the main mechanism for the protection of lung tissues from elastase injury.