The nature of chronic rejection after lung transplantation: a murine orthotopic lung transplant study

Chronic rejection; Lung transplantation; Mouse modelRechazo crónico; Trasplante de pulmón; Modelo de ratónRebuig crònic; Trasplantament de pulmó; Model de ratolíIntroduction: Chronic rejection is a major complication post-transplantation. Within lung transplantation, chronic rejection was considered as airway centred. Chronic Lung Allograft Dysfunction (CLAD), defined to cover all late chronic complications, makes it more difficult to understand chronic rejection from an immunological perspective. This study investigated the true nature, timing and location of chronic rejection as a whole, within mouse lung transplantation. Methods: 40 mice underwent an orthotopic left lung transplantation, were sacrificed at day 70 and evaluated by histology and in vivo µCT. For timing and location of rejection, extra grafts were sacrificed at day 7, 35, 56 and investigated by ex vivo µCT or single cell RNA (scRNA) profiling. Results: Chronic rejection originated as innate inflammation around small arteries evolving toward adaptive organization with subsequent end-arterial fibrosis and obliterans. Subsequently, venous and pleural infiltration appeared, followed by airway related bronchiolar folding and rarely bronchiolitis obliterans was observed. Ex vivo µCT and scRNA profiling validated the time, location and sequence of events with endothelial destruction and activation as primary onset. Conclusion: Against the current belief, chronic rejection in lung transplantation may start as an arterial response, followed by responses in venules, pleura, and, only in the late stage, bronchioles, as may be seen in some but not all patients with CLAD.The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. BV, WJ, and GG-R are supported by KU Leuven (C16/19/005; C24/15/030). DEVR is supported by the Broere Foundation. SM and RV are Senior Clinical Research Fellows of the Research Foundation Flanders (FWO; 12G8715N) and are supported by a UZ Leuven research grant (STG15/023). JK, ArV, and VG are Junior Research Fellows of the Research Foundation Flanders (1198920N and 1102020N). SM is supported by grants from UZ Leuven (KOOR) and KU Leuven (C1 funding). GV acknowledges funding by KU Leuven IF (C24/17/061 and STG/15/024)

A Comprehensive Review on the Surgical Aspect of Lung Transplant Models in Mice and Rats

Lung transplantation improves the outcome and quality of life of patients with end-stage pulmonary disease. However, the procedure is still hampered by the lack of suitable donors, the complexity of the surgery, and the risk of developing chronic lung allograft dysfunction. Over the past decades, translational experiments in animal models have led to a better understanding of physiology and immunopathology following the lung transplant procedure. Small animal models (e.g., rats and mice) are mostly used in experiments regarding immunology and pathobiology and are preferred over large animal models due to the ethical aspects, the cost-benefit balance, and the high throughput possibility. In this comprehensive review, we summarize the reported surgical techniques for lung transplantation in rodent models and the management of perioperative complications. Furthermore, we propose a guide to help identify the appropriate species for a given experiment and discuss recent experimental findings in small animal lung transplant models

Allogeneic Hematopoietic Stem Cell Transplantation After Prior Lung Transplantation for Hereditary Pulmonary Alveolar Proteinosis: A Case Report

Pulmonary alveolar proteinosis (PAP) is a rare, diffuse lung disorder characterized by surfactant accumulation in the small airways due to defective clearance by alveolar macrophages, resulting in impaired gas exchange. Whole lung lavage is the current standard of care treatment for PAP. Lung transplantation is an accepted treatment option when whole lung lavage or other experimental treatment options are ineffective, or in case of extensive pulmonary fibrosis secondary to PAP. A disadvantage of lung transplantation is recurrence of PAP in the transplanted lungs, especially in hereditary PAP. The hereditary form of PAP is an ultra-rare condition caused by genetic mutations in genes encoding for the granulocyte macrophage-colony stimulating factor (GM-CSF) receptor, and intrinsically affects bone marrow derived-monocytes, which differentiate into macrophages in the lung. Consequently, these macrophages typically display disrupted GM-CSF receptor-signaling, causing defective surfactant clearance. Bone marrow/hematopoietic stem cell transplantation may potentially reverse the lung disease in hereditary PAP. In patients with hereditary PAP undergoing lung transplantation, post-lung transplant recurrence of PAP may theoretically be averted by subsequent hematopoietic stem cell transplantation, which results in a graft-versus-disease (PAP) effect, and thus could improve long-term outcome. We describe the successful long-term post-transplant outcome of a unique case of end-stage respiratory failure due to hereditary PAP-induced pulmonary fibrosis, successfully treated by bilateral lung transplantation and subsequent allogeneic hematopoietic stem cell transplantation. Our report supports treatment with serial lung and hematopoietic stem cell transplantation to improve quality of life and prolong survival, without PAP recurrence, in selected patients with end-stage hereditary PAP

Bos op arme gronden

Onder arme groeiplaatsen worden vooral de zandgronden verstaan. In Nederland liggen ze in het oosten en het zuiden van het land en ze lopen door naar de zandgronden in het noorden van Vlaanderen. De duinengordel langs de Noordzeekust behoort ook tot deze categorie. Zandgronden kunnen verder ingedeeld worden volgens hun geologische ontstaanswijze. Er kan onderscheid gemaakt worden tussen afzettingen door zee, rivieren of de wind, die bovendien uit het tertiair of het quartair tijdvak kunnen dateren. Zowel in Vlaanderen als Nederland ligt het grootste deel van het huidige bosareaal op de arme zandgronden: in Vlaanderen is het 60% van het totale areaal (90.000 ha) en in Nederland 86% (270.000 ha)

Bosomvorming: noodzaak en praktijk van een effectgerichte maatregel tegen verzuring en vermesting

B

Allometric biomass equations for Scots pine (Pinus sylvestris L.) seedlings during the first years of establishment in dense natural regeneration

International audienceA dense natural regeneration of Scots pine (Pinus sylvestris L.) exhibits a considerable biomass build-up in the first four years, with amounts of 7.03 Mg ha-1 for aboveground biomass, and 0.88 Mg ha-1 for coarse root biomass (> 1 mm). Power equations were developed, which relate collar diameter (ranging from 0.3 to 2.7 cm) and height to total aboveground and coarse root biomass of two, three and four-year-old seedlings in a regeneration of 16 seedlings m-2 at one site in Belgium. During the first years of establishment, seedling allometry changes with age, whilst the density remains constant. Biomass equations developed for one of the three ages can produce biased predictions for the other ages. Even when an equation is based on data for all ages and information on height is included, age still has to be considered as a potential predictor variable. For pooled ages, linear regression after logarithmic transformation of the power equation, selected other predictors than weighted non-linear regression. The former approach indicated significant interactions between predictors, while the latter does not reveal interactions.Équations d'allométrie de biomasse pour semis de pin sylvestre (Pinus sylvestris L.) dans les premières années d'établissement d'une régénération naturelle dense. Une régénération naturelle dense de pin sylvestre (Pinus sylvestris L.) montre une accroissement considérable de biomasse dans les quatre premières années, avec des quantités de 7,03 Mg ha-1 pour la biomasse aérienne et 0,88 Mg ha-1 pour la biomasse des grosses racines (> 1 mm). Des équations de type puissance mettant en relation le diamètre au niveau du collet racinaire (intervalle de 0,3 à 2,7 cm) et la hauteur avec la biomasse aérienne et la biomasse des grosses racines de semis de pin sylvestre âgés de deux, trois et quatre ans ont été développées dans une régénération d'une densité de 16 semis m-2 sur un site en Belgique. Entre la deuxième et la quatrième année, à densité stationnaire, la relation d'allométrie des semis change avec l'âge. Les équations de biomasse développées pour les semis d'un même âge, peuvent produire des prédictions erronées pour les autres âges. Même en utilisant des donnés de tous les âges et la variable hauteur, l'âge doit être considéré comme une variable potentielle dans l'analyse de régression. En utilisant des donnés de tous les âges, l'analyse de régression linéaire a retenu différentes variables que l'analyse de régression non-linéaire pondérée. La première désignait des interactions significatives, tandis que la dernière ne considère pas les interactions