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.

Autor: Schnapper A; Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.; REBIRTH (From Regenerative Biology to Reconstructive Therapy), Cluster of Excellence, Hannover, Germany., Christmann A; Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.; REBIRTH (From Regenerative Biology to Reconstructive Therapy), Cluster of Excellence, Hannover, Germany., Knudsen L; Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.; REBIRTH (From Regenerative Biology to Reconstructive Therapy), Cluster of Excellence, Hannover, Germany., Rahmanian P; Department of Cardiothoracic Surgery, Heart Center, University of Cologne, Cologne, Germany., Choi YH; Department of Cardiothoracic Surgery, Heart Center, University of Cologne, Cologne, Germany.; Center of Molecular Medicine, University of Cologne, Cologne, Germany., Zeriouh M; Department of Cardiothoracic Surgery, Heart Center, University of Cologne, Cologne, Germany., Karavidic S; Department of Cardiothoracic Surgery, Heart Center, University of Cologne, Cologne, Germany., Neef K; Department of Cardiothoracic Surgery, Heart Center, University of Cologne, Cologne, Germany.; Center of Molecular Medicine, University of Cologne, Cologne, Germany., Sterner-Kock A; Center for Experimental Medicine, University of Cologne, Cologne, Germany., Guschlbauer M; Center for Experimental Medicine, University of Cologne, Cologne, Germany.; Decentral Animal Facility, University of Cologne, Cologne, Germany., Hofmaier F; Center for Experimental Medicine, University of Cologne, Cologne, Germany., Maul AC; Center for Experimental Medicine, University of Cologne, Cologne, Germany., Wittwer T; Department of Cardiothoracic Surgery, Heart Center, University of Cologne, Cologne, Germany.; Center of Molecular Medicine, University of Cologne, Cologne, Germany., Wahlers T; Department of Cardiothoracic Surgery, Heart Center, University of Cologne, Cologne, Germany.; Center of Molecular Medicine, University of Cologne, Cologne, Germany., Mühlfeld C; Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.; REBIRTH (From Regenerative Biology to Reconstructive Therapy), Cluster of Excellence, Hannover, Germany.; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany., Ochs M; Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.; REBIRTH (From Regenerative Biology to Reconstructive Therapy), Cluster of Excellence, Hannover, Germany.; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany.
Jazyk: angličtina
Zdroj: Journal of anatomy [J Anat] 2018 Feb; Vol. 232 (2), pp. 283-295. Date of Electronic Publication: 2017 Nov 28.
DOI: 10.1111/joa.12747
Abstrakt: 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 × 10 6 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.
(© 2017 Anatomical Society.)
Databáze: MEDLINE
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