Lung Organoids and Perinatal Stem Cells
Leader of this group:
PhD MD Mariann Bentsen
Our research group has developed a novel human lung organoid model that are mimicking preterm lungs. Further development of this model to mimic lung disease of prematurity (bronchopulmonary dysplasia, BPD), the most common problem following extremely preterm birth, is currently our main focus.
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A human model mimicking BPD lungs will increase our understanding of the pathogenic mechanisms causing this complication, and is also essential for the development and efficacy testing of novel therapeutics. Our research group works to examine the effect of perinatal stem cells found in the umbilical cord tissue, with a long-term goal of conducting a clinical trial testing the effect of autologous umbilical cord cells.
Our research is in an establishment phase, and our group is working in close collaboration with the “Tissue Engineering Research Group”, the “Cellular Networks Research Group”, and “Research Group for Pregnancy, Fetal Development and Birth” at the University of Bergen, as well as Mohn Research Centre for Regenerative Medicine, Haukeland University Hospital.
Histology of human alveolar lung organoids generated by our group.
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a) Two-row/pseudo-multi-row of cells (green arrow), similar to the epithelial lining of the airway tree in the human early, pseudoglandular phase.
b) Single-row epithelial lining with subnuclear vacuolization (blue arrow), similar to the epithelium in the pseudo-glandular/early canalicular phase. Green arrow: layer of cubic cells resembles human embryonic lungs in the canalicular phase.
c ) Organoids with apical vacuolization and ciliation (bronchiolar phenotype) (thin arrows) and flattening of cells as by alveolar type 1 pneumocyte express proximal-distal differentiation.
Publications
1
Hoareau L, Engelsen AST, Aanerud M, Ramnefjell MP, Salminen PR, Gärtner F, Halvorsen T, Raeder H and Bentsen MHL. Induction of alveolar and bronchiolar phenotypes in human lung organoids. Physiol Rep. 2021
2
Ekanger CT, Zhou F, Bohan D, Lotsberg ML, Ramnefjell M, Hoareau L, Røsland GV, Lu N, Aanerud M, Gärtner F, Salminen PR, Bentsen MHL, Halvorsen T, Ræder H, Akslen LA, Langeland N, Cox R, Maury W, Stuhr LEB, Lorens JB and Engelsen AST. Human organotypic airway and lung organoids susceptible to infection with respiratory viruses including SARS-CoV-2. Frontiers in Cellular and Infection Microbiology. Mar. 2022.