Differential effects of the cystic fibrosis lung inflammatory environment on mesenchymal stromal cells.
Differential effects of the cystic fibrosis lung inflammatory environment on mesenchymal stromal cells.
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DOI：
10.1152/ajplung.00218.2020
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发表时间：
2020-12-01
期刊：
影响因子：
--
通讯作者：
Rolandsson Enes S
中科院分区：
文献类型：
--
作者：
Abreu SC;Hampton TH;Hoffman E;Dearborn J;Ashare A;Singh Sidhu K;Matthews DE;McKenna DH;Amiel E;Barua J;Krasnodembskaya A;English K;Mahon B;Dos Santos C;Cruz FF;Chambers DC;Liu KD;Matthay MA;Cramer RA;Stanton BA;Rocco PRM;Wargo MJ;Weiss DJ;Rolandsson Enes S
越来越多的证据表明，人类间充质基质细胞（MSC）修改其在体内的抗炎作用，这取决于所遇到的特定炎症环境。更好地理解这一点对于完善基于MSC的细胞疗法治疗肺部和其他疾病至关重要。使用囊性纤维化（CF）肺病急性加重作为模型，将离体MSC暴露于临床支气管肺泡灌洗液（BALF）样品（作为体内临床肺环境的替代物）对MSC活力、基因表达、分泌的细胞因子和线粒体功能的影响与从健康志愿者收集的BALF的影响进行比较。培养为曲霉菌属（Asp）阳性的CF BALF样品诱导MSC快速死亡，通常在暴露后数小时内。进一步的分析表明真菌毒素gliotoxin作为一种潜在的介质，有助于CF BALF诱导的MSC死亡。暴露于Asp+或Asp-CF BALF样本的MSC的RNA测序分析鉴定了许多差异表达的转录本，包括参与干扰素信号传导、抗菌基因表达和细胞死亡的转录本。毒性与细菌性肺部感染无关。这些结果表明，在曲霉菌存在的情况下，基于MSC的细胞疗法用于CF或其他肺部疾病的潜在用途可能是不必要的。
Growing evidence demonstrates that human mesenchymal stromal cells (MSCs) modify their in vivo anti-inflammatory actions depending on the specific inflammatory environment encountered. Understanding this better is crucial to refine MSC-based cell therapies for lung and other diseases. Using acute exacerbations of cystic fibrosis (CF) lung disease as a model, the effects of ex vivo MSC exposure to clinical bronchoalveolar lavage fluid (BALF) samples, as a surrogate for the in vivo clinical lung environment, on MSC viability, gene expression, secreted cytokines, and mitochondrial function were compared with effects of BALF collected from healthy volunteers. CF BALF samples that cultured positive for Aspergillus sp. (Asp) induced rapid MSC death, usually within several hours of exposure. Further analyses suggested the fungal toxin gliotoxin as a potential mediator contributing to CF BALF-induced MSC death. RNA sequencing analyses of MSCs exposed to either Asp+ or Asp− CF BALF samples identified a number of differentially expressed transcripts, including those involved in interferon signaling, antimicrobial gene expression, and cell death. Toxicity did not correlate with bacterial lung infections. These results suggest that the potential use of MSC-based cell therapies for CF or other lung diseases may not be warranted in the presence of Aspergillus.
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影响因子：
6
作者：
Cruz FF;Borg ZD;Goodwin M;Coffey AL;Wagner DE;Rocco PR;Weiss DJ
通讯作者：
Weiss DJ
DOI：
10.1016/s2213-2600(18)30418-1
发表时间：
2019-03
期刊：
The Lancet. Respiratory medicine
影响因子：
--
作者：
Matthay MA;Calfee CS;Zhuo H;Thompson BT;Wilson JG;Levitt JE;Rogers AJ;Gotts JE;Wiener-Kronish JP;Bajwa EK;Donahoe MP;McVerry BJ;Ortiz LA;Exline M;Christman JW;Abbott J;Delucchi KL;Caballero L;McMillan M;McKenna DH;Liu KD
通讯作者：
Liu KD
影响因子：
6
作者：
Bustos, Martha L.;Huleihel, Luai;Rojas, Mauricio
通讯作者：
Rojas, Mauricio
影响因子：
2.7
作者：
Ideozu, Justin E.;Rangaraj, Vittobai;Levy, Hara
通讯作者：
Levy, Hara
影响因子：
3.1
作者：
Lewis, RE;Wiederhold, NP;Prince, RA
通讯作者：
Prince, RA