21EBTA. Bioengineering iLUNGs - Building scalable, integrated, multicellular and personalised human in vitro LUNGs

The human respiratory system exists to perform gas exchange and thus support life. The entire cellular surface of the lung is continuous with air from the main airways, to tree-like branched airways and the sacs where gas exchange happens - these are called alveoli.

Although there has been great progress in laboratory models of individual parts of the lung, they do not have this feature of functional evolution from the airways to the the alveoli. The absence of integrated models has hampered progress in understanding lung physiology and what happens in lung disease. Further, key societal issues like the development of new inhaled treatments for specific diseases and an understanding of what environmental pollution does to the lung would be really enhanced by better models.

In this project, we aim to engineer a living model of the human lung where the airway to the alveolar sacs are fully connected and functional. We call it the iLUNG. A key advantage of our work is that we will use multiple cell types from an individual patient to create them. This means that they will be truly individualised "mini-lungs" and will therefore hopefully reflect the disease associated with the person that we grew the cells from. This opens up the possibility of more targeted treatments for lung disease as well new possibilities to understand basic lung biology and how different types of cells in the lung talk to each other.

We have put together a great team of lung bioengineers for this proposal and have the engineering and scientific infrastructure as well as access to patients to make this project deliverable. We are tremendously excited by the potential of the iLUNG and are fully motivated to train the next generation of lung bioengineers. Finally we are clear that we want this technology to be used widely in academia and industry and eventually be both a scientific and commercial success.

The human respiratory system exists to perform gas exchange and thus support life. The entire epithelial surface is continuous with ambient air and is functionally adapted to its role - conducting airflow through tapering tree-like branched airways that are eventually continuous with alveolar units in which a flattened epithelium is intimately associated with the capillary endothelium. To date there are no in vitro lung models which integrate the continuous changing epithelium to create a whole functional airway.
The lack of complex models has slowed progress in understanding lung biology and pathobiology. Although there has been progress in modelling discreet lung units, they do not emulate the 'in vivo' integrated whole.
We have assembled an outstanding team of lung bio-engineers from multiple disciplines committed to building iLUNGs - scalable, individualised in vitro models of the human respiratory system with profound potential for both discovery and applied science. The iLUNG will deliver a model of the human lower respiratory tract as an integrated anatomical entity - in which the "atmosphere" is connected to the gas exchange units via a continuous epithelial surface that seamlessly incorporates the functionally distinct units in the human airway.
This will be a platform technology - we will reproduce, at scale, a device which recreates the human respiratory tract, from the large airway to the distal alveoli. Crucially the multiple cell lineages that will be incorporated in an iLUNG will all come from a single individual, thus creating rational complex living models of an individual's lung.