Universität zu Köln

Schnapper, Anke, Christmann, Astrid, Knudsen, Lars ORCID: 0000-0002-7926-3879, Rahmanian, Parwis, Choi, Yeong-Noon, Zeriouh, Mohamed, Karavidic, Samira, Neef, Klaus, Sterner-Kock, Anja, Guschlbauer, Maria ORCID: 0000-0002-5401-4542, Hofmaier, Florian, Maul, Alexandra C., Wittwer, Thorsten, Wahlers, Thorsten, Muehlfeld, Christian and Ochs, Matthias (2018). 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. J. Anat., 232 (2). S. 283 - 296. HOBOKEN: WILEY. ISSN 1469-7580

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Abstract

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 x 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 mu m(3)) compared with the sham control group (median 0.814 mu m(3)). 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schnapper, Anke UNSPECIFIED UNSPECIFIED UNSPECIFIED Christmann, Astrid UNSPECIFIED UNSPECIFIED UNSPECIFIED Knudsen, Lars UNSPECIFIED orcid.org/0000-0002-7926-3879 UNSPECIFIED Rahmanian, Parwis UNSPECIFIED UNSPECIFIED UNSPECIFIED Choi, Yeong-Noon UNSPECIFIED UNSPECIFIED UNSPECIFIED Zeriouh, Mohamed UNSPECIFIED UNSPECIFIED UNSPECIFIED Karavidic, Samira UNSPECIFIED UNSPECIFIED UNSPECIFIED Neef, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Sterner-Kock, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Guschlbauer, Maria UNSPECIFIED orcid.org/0000-0002-5401-4542 UNSPECIFIED Hofmaier, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Maul, Alexandra C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wittwer, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Wahlers, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Muehlfeld, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Ochs, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-197539
DOI:	10.1111/joa.12747
Journal or Publication Title:	J. Anat.
Volume:	232
Number:	2
Page Range:	S. 283 - 296
Date:	2018
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1469-7580
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ISCHEMIA-REPERFUSION INJURY; INTERNATIONAL SOCIETY; EXOGENOUS SURFACTANT; ISCHEMIA/REPERFUSION INJURY; ALLOGRAFT DYSFUNCTION; GROWTH-FACTOR; ADULT LUNG; II CELLS; PRESERVATION; DEATH Multiple languages Anatomy & Morphology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19753