Tracking of Infused Mesenchymal Stem Cells in Injured Pulmonary Tissue inAtm-Deficient Mice
Tracking of Infused Mesenchymal Stem Cells in Injured Pulmonary Tissue inAtm-Deficient Mice
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DOI：
10.3390/cells9061444
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发表时间：
2020-06-01
期刊：
影响因子：
6
通讯作者：
Schubert, Ralf
中科院分区：
文献类型：
--
作者：
Baer, Patrick C.;Sann, Julia;Schubert, Ralf
肺功能衰竭是人类染色体不稳定综合征共济失调-毛细血管扩张症（A-T）发病和死亡的主要原因。主要表型包括反复呼吸道感染和支气管扩张、误吸、呼吸肌异常、间质性肺病和肺纤维化。目前，还没有有效的肺部治疗A-T存在。利用脂肪间充质干细胞（ASCs）进行细胞治疗可能是一种有前途的组织再生方法。本项目的目的是研究ASC是否迁移到Atm缺陷小鼠的损伤肺实质中，作为A-T期间早期组织损伤的指示。因此，从荧光素酶转基因小鼠（mASCs）分离的ASCs静脉内移植到Atm缺陷型和野生型小鼠。使用体内生物发光成像（BLI）监测细胞的保留动力学，并通过使用定量实时聚合酶链反应（qRT-PCR）的后续验证来完成。体内成像和qPCR结果表明，与野生型小鼠相比，Atm缺陷小鼠的肺实质中移植的mASC的迁移伴随着显著更长的保留时间。总之，我们的研究表明ATM缺陷小鼠的肺实质中存在早期损伤。此外，我们的数据进一步证明，基于DNA酶的PCR与BLI的组合是在炎性肺病（如A-T）模型中移植后追踪mASC的关键工具。
Pulmonary failure is the main cause of morbidity and mortality in the human chromosomal instability syndrome Ataxia-telangiectasia (A-T). Major phenotypes include recurrent respiratory tract infections and bronchiectasis, aspiration, respiratory muscle abnormalities, interstitial lung disease, and pulmonary fibrosis. At present, no effective pulmonary therapy for A-T exists. Cell therapy using adipose-derived mesenchymal stromal/stem cells (ASCs) might be a promising approach for tissue regeneration. The aim of the present project was to investigate whether ASCs migrate into the injured lung parenchyma ofAtm-deficient mice as an indication of incipient tissue damage during A-T. Therefore, ASCs isolated from luciferase transgenic mice (mASCs) were intravenously transplanted intoAtm-deficient and wild-type mice. Retention kinetics of the cells were monitored using in vivo bioluminescence imaging (BLI) and completed by subsequent verification using quantitative real-time polymerase chain reaction (qRT-PCR). The in vivo imaging and the qPCR results demonstrated migration accompanied by a significantly longer retention time of transplanted mASCs in the lung parenchyma ofAtm-deficient mice compared to wild type mice. In conclusion, our study suggests incipient damage in the lung parenchyma ofAtm-deficient mice. In addition, our data further demonstrate that a combination of luciferase-based PCR together with BLI is a pivotal tool for tracking mASCs after transplantation in models of inflammatory lung diseases such as A-T.