Pretreatment with bone marrow-derived mesenchymal stromal cell-conditioned media confers pulmonary ischemic tolerance.
Pretreatment with bone marrow-derived mesenchymal stromal cell-conditioned media confers pulmonary ischemic tolerance.
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DOI：
10.1016/j.jtcvs.2015.11.043
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Mulligan MS
中科院分区：
文献类型：
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作者：
Hwang B;Liles WC;Waworuntu R;Mulligan MS
基于间充质基质细胞的疗法已经证明在治疗多种疾病中的功效。尽管有潜在的好处，但临床使用仍需要克服重大障碍。我们描述了一种基于无细胞的免疫治疗方法，通过使用间充质基质细胞条件培养基（MSC-CM）诱导肺缺血耐受。MSC在我们建立的肺缺血再灌注模型中，我们在损伤前30分钟用MSC-CM预处理。为了确定肺损伤的程度，我们评估了肺血管通透性、促炎细胞因子和BAL中细胞浸润以及组织病理学的变化。巨噬细胞和T细胞亚群通过免疫组织化学进行评估。MSC-CM预处理可减轻肺缺血再灌注损伤（LIRI）。这种保护的特征在于促炎细胞因子的显著减少、浸润性炎性细胞的减少以及M2样巨噬细胞和调节性T细胞的增加。无细胞MSC-CM疗法赋予肺缺血耐受性。这种疗法利用旁分泌因子，通过免疫调节驻留和浸润细胞亚群中的炎症反应提供有益的保护作用。
Mesenchymal stromal cell based therapies have demonstrated efficacy in treating a variety of diseases. Despite the potential benefits, there are still significant hurdles that need to be overcome for clinical use. We describe a cell-free based immunotherapy approach for inducing pulmonary ischemic tolerance by using mesenchymal stromal cell conditioned media (MSC-CM). MSC In our well established lung ischemia reperfusion model, we pretreated with MSC-CM 30 minutes prior to injury. To determine degree of lung injury, we assessed for changes in lung vascular permeability, proinflammatory cytokines and cellular infiltrates in BAL, and histopathology. Macrophage and T cell subsets were assessed by immunohistochemistry. Pretreatment with MSC-CM conferred protection against lung ischemia reperfusion injury (LIRI). This protection is characterized by a significant reduction in proinflammatory cytokines, decrease in infiltrating inflammatory cells, and increases in M2-like macrophages and regulatory T cells. Cell-free MSC-CM therapy confers pulmonary ischemic tolerance. This therapeutic utilizes paracrine factors that provide beneficial protective effects by immunomodulating the inflammatory response in resident and infiltrating cell subsets.