Stereological assessment of the blood‐air barrier and the surfactant system after mesenchymal stem cell pretreatment in a porcine non‐heart‐beating donor model for lung transplantation-猫眼课题宝

DOI：

10.1111/joa.12747

发表时间：

2018-02

期刊：

Journal of Anatomy

影响因子：

2.4

通讯作者：

中科院分区：

医学3区

文献类型：

作者：

A. Schnapper;A. Christmann;L. Knudsen;P. Rahmanian;Yeong-Hoon Choi;M. Zeriouh;Samira Karavidic;K. Neef;A. Sterner-Kock;M. Guschlbauer;F. Hofmaier;A. Maul;T. Wittwer;T. Wahlers;C. Mühlfeld;M. Ochs

更频繁地利用无心跳供体（NHBD）器官进行肺移植有可能缓解供体器官短缺的问题。特别是对于不受控制的NHBD，存在缺血/再灌注（IR）损伤相关移植物损伤或功能障碍风险的担忧。由于其免疫调节和组织重塑特性，骨髓间充质干细胞（MSC）被怀疑在同种异体移植物的短期和长期存活和功能方面发挥有益作用。因此，MSC给药可能代表了NHBD器官有希望的预处理策略。为了研究热缺血和MSC应用的初始效果，产生了大型动物肺移植模型，并对移植肺的结构器官组成进行了体视学分析，特别是关于血气屏障和表面活性剂系统。在本研究中，分析了猪肺（n = 5/组）。第1组为假手术对照组。在组2-4的猪中，诱导心脏骤停，随后在室温下通气缺血3小时。在第3组和第4组中，在缺血的最后10分钟，分别通过肺动脉和支气管内血管内注射50 × 106个MSC。移植左肺，然后再灌注4 h。然后，将肺灌注固定并处理用于光学和电子显微镜检查。对样本的IR损伤相关结构参数进行体视学分析，包括实质成分、肺泡间隔成分、肺泡内水肿以及细胞内和肺泡内表面活性物质池的体积密度和绝对体积。此外，测定了板层体的体积加权平均体积（lbs）及其轮廓尺寸分布。定性和定量评估显示，3小时的通气性热缺血耐受性良好，未引起IR损伤的组织学或超微结构体征。然而，热缺血影响表面活性剂系统。与假手术对照组（中位数0.814 μm³）相比，缺血组（第2-4组的组中位数：0.180-0.373 μm³）的lbs体积加权平均体积显著降低（P = 0.024）。这是由于大lb型材数量较少（尺寸类别5-15）。相比之下，肺泡内表面活性剂系统没有显著改变。在该短期模型中，比较单独缺血（第2组）或缺血加应用MSC（第3组和第4组）未发现显著差异。

More frequent utilization of non‐heart‐beating donor (NHBD) organs for lung transplantation has the potential to relieve the shortage of donor organs. In particular with respect to uncontrolled NHBD, concerns exist regarding the risk of ischaemia/reperfusion (IR) injury‐related graft damage or dysfunction. Due to their immunomodulating and tissue‐remodelling properties, bone‐marrow‐derived mesenchymal stem cells (MSCs) have been suspected of playing a beneficial role regarding short‐ and long‐term survival and function of the allograft. Thus, MSC administration might represent a promising pretreatment strategy for NHBD organs. To study the initial effects of warm ischaemia and MSC application, a large animal lung transplantation model was generated, and the structural organ composition of the transplanted lungs was analysed stereologically with particular respect to the blood–gas barrier and the surfactant system. In this study, porcine lungs (n = 5/group) were analysed. Group 1 was the sham‐operated control group. In pigs of groups 2–4, cardiac arrest was induced, followed by a period of 3 h of ventilated ischaemia at room temperature. In groups 3 and 4, 50 × 106 MSCs were administered intravascularly via the pulmonary artery and endobronchially, respectively, during the last 10 min of ischaemia. The left lungs were transplanted, followed by a reperfusion period of 4 h. Then, lungs were perfusion‐fixed and processed for light and electron microscopy. Samples were analysed stereologically for IR injury‐related structural parameters, including volume densities and absolute volumes of parenchyma components, alveolar septum components, intra‐alveolar oedema, and the intracellular and intra‐alveolar surfactant pool. Additionally, the volume‐weighted mean volume of lamellar bodies (lbs) and their profile size distribution were determined. Three hours of ventilated warm ischaemia was tolerated without eliciting histological or ultrastructural signs of IR injury, as revealed by qualitative and quantitative assessment. However, warm ischaemia influenced the surfactant system. The volume‐weighted mean volume of lbs was reduced significantly (P = 0.024) in groups subjected to ischaemia (group medians of groups 2–4: 0.180–0.373 μm³) compared with the sham control group (median 0.814 μm³). This was due to a lower number of large lb profiles (size classes 5–15). In contrast, the intra‐alveolar surfactant system was not altered significantly. No significant differences were encountered comparing ischaemia alone (group 2) or ischaemia plus application of MSCs (groups 3 and 4) in this short‐term model.

Stereological assessment of the blood‐air barrier and the surfactant system after mesenchymal stem cell pretreatment in a porcine non‐heart‐beating donor model for lung transplantation

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