Localization of Exogenous Mesenchymal Stem Cells in a Pig Model of Lung Transplantation
Localization of Exogenous Mesenchymal Stem Cells in a Pig Model of Lung Transplantation
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DOI：
10.1055/s-0037-1607051
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发表时间：
2017-10
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通讯作者：
T. Piatkowski;C. Brandenberger;P. Rahmanian;Yeong-Hoon Choi;M. Zeriouh;A. Sabashnikov;T. Wittwer;T. Wahlers;M. Ochs;C. Mühlfeld
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作者：
T. Piatkowski;C. Brandenberger;P. Rahmanian;Yeong-Hoon Choi;M. Zeriouh;A. Sabashnikov;T. Wittwer;T. Wahlers;M. Ochs;C. Mühlfeld
摘要背景间充质干细胞（MSCs）在治疗急性肺损伤方面具有巨大的潜力。本研究提供了一个详细的免疫组织化学和体视学分析的定位和分布的外源性MSC在猪模型肺移植后血管内或支气管内应用。方法用DiI标记人骨髓间充质干细胞，分别经血管内或支气管内注入热缺血3 h和冷缺血3 h的供体猪肺。将左肺移植至受体猪，并在固定前再灌注4小时。在缺血时间后立即固定右供体肺用于显微镜分析。结果两种途径给药后，在肺组织中发现了相似数量的外源性MSC。在每只动物体内，MSC分布的异质性在左肺和右肺以及每个肺的不同叶中都很高。支气管内应用后，MSC被发现在肺泡和支气管/细支气管腔，而血管内给药后，它们主要被观察到在血管中。结论虽然外源性MSC可以通过支气管内或血管内应用，但在肺内的分布不均匀，这可能需要改善更均匀分布的策略。
Abstract Background Mesenchymal stem cells (MSCs) have a great potential for the treatment of acute lung injury. This study provides a detailed immunohistochemical and stereological analysis of the localization and distribution of exogenous MSC in a pig model of lung transplantation after intravascular or endobronchial application. Methods MSC derived from human bone marrow were labeled by DiI and administered intravascularly or endobronchially to the lungs of donor pigs after a period of 3 hours warm and 3 hours cold ischemia. The left lung was transplanted to a recipient pig and reperfused for 4 hours before fixation. The right donor lung was fixed for microscopic analysis directly after the ischemia time. Results After both administration routes, a similar number of exogenous MSC was found in the lungs. Within each animal, the heterogeneity of MSC distribution was high both with respect to left and right lung as well as to the different lobes of each lung. After endobronchial application, MSC were found in alveolar and bronchial/bronchiolar lumen, whereas after intravascular administration, they were mainly observed in blood vessels. Conclusion Although the administration of exogenous MSC is possible by endobronchial or intravascular application, it yields a heterogeneous distribution in the lungs which may warrant strategies to improve a more homogeneous distribution.