21 March 2022

Bronchi in a test tube

Laboratory tests of the respiratory organs usually require the collection of large tissue samples from humans or animals. Researchers at the Faculty of Medicine of the University of Freiburg in collaboration with American colleagues from the University of California at San Francisco have created organoids of tracheobronchial tissue from just a few living cells. As the cells develop, they form a three-dimensional structure with cilia on the surface characteristic of the inner surface of the respiratory tract. These organoids may be useful for future research on respiratory diseases, drug development, or personalized medicine.

The method by which the researchers achieved the organization of cells into three-dimensional organoids is relatively simple and inexpensive and reproduces important biological aspects of lung tissue. They isolated human tracheobronchial epithelial cells, cultured them in mixed matrix components and supplemented them with two messengers on day 14: an agonist of the Wnt signaling pathway and an antagonist of bone morphogenetic protein. After that, the cells formed three-dimensional organoids.

Previously, this process consisted of many stages, for example, cells taken from a person first had to be returned to an embryo-like state using complex methods. In addition, the outer side of the organoid tissue was always directed inward and looked much less like a natural tissue. The new method makes it possible to obtain differentiated tracheobronchospheres with externally oriented cilia, providing a model for studying the function of cilia, the pathogenesis of cilipathies and the interaction of pathogens with the mucous membrane of the respiratory tract.

bronchi.jpg

Human tracheobronchial epithelial cells organized into tracheobronchospheres with cilia (purple) and various cell types, for example, secretory goblet cells (yellow).

Individual therapy

The researchers took cells from patients with cystic fibrosis, and characteristically altered organoids were formed from them. This gives hope that in the future this simplified method will allow to grow bronchial organoids of specific patients in order to check in advance whether this or that therapy will be effective or not. In addition, organoids can be used to study the development of healthy tracheobronchial tissue and the influence of genetic factors on this process.

An alternative to animal models

Healthy development of the respiratory system and genetic diseases have often been studied in animal models. The new method is able to replace some of these studies by growing tissue in three-dimensional form in a test tube.

Article by C.A.Boecking et al. A simple method to generate human airway epithelial organoids with externally-oriented apical membranes is published in the American Journal of Physiology.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Freiburg: Lung Tissue from the Lab.


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