Zhang Shijia, Danchuk Svitlana D, Bonvillain Ryan W, Xu Beibei, Scruggs Brittni A, Strong Amy L, Semon Julie A, Gimble Jeffrey M, Betancourt Aline M, Sullivan Deborah E, Bunnell Bruce A
Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA; Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Stem Cells. 2014 Jun;32(6):1616-28. doi: 10.1002/stem.1632.
Adipose-derived stromal/stem cells (ASCs) have anti-inflammatory as well as immunosuppressive activities and are currently the focus of clinical trials for a number of inflammatory diseases. Acute lung injury (ALI) is an inflammatory condition of the lung for which standard treatment is mainly supportive due to lack of effective therapies. Our recent studies have demonstrated the ability of both human ASCs (hASCs) and mouse ASCs (mASCs) to attenuate lung damage and inflammation in a rodent model of lipopolysaccharide-induced ALI, suggesting that ASCs may also be beneficial in treating ALI. To better understand how ASCs may act in ALI and to elucidate the mechanism(s) involved in ASC modulation of lung inflammation, gene expression analysis was performed in ASC-treated (hASCs or mASCs) and control sham-treated lungs. The results revealed a dramatic difference between the expression of anti-inflammatory molecules by hASCs and mASCs. These data show that the beneficial effects of hASCs and mASCs in ALI may result from the production of different paracrine factors. Interleukin 6 (IL-6) expression in the mASC-treated lungs was significantly elevated as compared to sham-treated controls 20 hours after delivery of the cells by oropharyngeal aspiration. Knockdown of IL-6 expression in mASCs by RNA interference abrogated most of their therapeutic effects, suggesting that the anti-inflammatory properties of mASCs in ALI are explained, at least in part, by activation of IL-6 secretion.
脂肪来源的基质/干细胞（ASC）具有抗炎和免疫抑制活性，目前是多种炎症性疾病临床试验的重点。急性肺损伤（ALI）是一种肺部炎症性疾病，由于缺乏有效治疗方法，其标准治疗主要是支持性治疗。我们最近的研究表明，人ASC（hASC）和小鼠ASC（mASC）都能够减轻脂多糖诱导的ALI啮齿动物模型中的肺损伤和炎症，这表明ASC在治疗ALI方面可能也有益处。为了更好地了解ASC在ALI中可能的作用方式，并阐明ASC调节肺部炎症所涉及的机制，我们对接受ASC治疗（hASC或mASC）的肺和假手术对照肺进行了基因表达分析。结果显示，hASC和mASC在抗炎分子表达上存在显著差异。这些数据表明，hASC和mASC在ALI中的有益作用可能源于不同旁分泌因子的产生。通过口咽抽吸给予细胞20小时后，与假手术对照相比，mASC治疗的肺中白细胞介素6（IL-6）表达显著升高。通过RNA干扰敲低mASC中的IL-6表达消除了其大部分治疗效果，这表明mASC在ALI中的抗炎特性至少部分是由IL-6分泌的激活所解释的。
