A team at University College London is collecting and studying human lung tissue from foetuses between 20 weeks and birth—a developmental period that scientists have largely ignored because it is so difficult to access. This matters because premature birth is the leading cause of newborn death and long-term disability, and the root problem is almost always an immature lung that cannot yet exchange oxygen and carbon dioxide. Current treatments like steroids help a little but do not prevent lasting damage. The same lack of basic knowledge about how lungs finish developing also blocks progress in regenerating lung tissue for adults with end-stage disease. The researchers have already built a 3D culture system that grows human lung tissue in a dish, and they have mapped how immune cells interact with the developing lung up to 20 weeks. Now they will extend that work into the final months of pregnancy, studying how the lung lining, blood vessels, and immune system mature together to form a working gas-exchange unit. They will also create a tissue bank for other groups studying late foetal organ development. This is fundamental science with no immediate clinical application, but understanding the final stages of lung maturation could eventually point to new ways to help premature babies survive without lifelong breathing problems, and to strategies for repairing damaged adult lungs.
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Our understanding of how the lung develops is very poor. Addressing this is really important because we can work out how to help premature babies and how to regenerate lungs to help those with severe lung disease. End-stage lung disease of any cause is a major global health problem. On the other hand, the death rate and problems arising from premature birth are mostly caused by the fact that the lung is too immature or underdeveloped to function as opposed to in healthy term babies. This is despite the use of some treatments such as steroids which do not overcome the long-term effects of premature birth on lung function as an adult. I have already made important discoveries to understand lung development. This was made using human embryonic and foetal lungs up to 20 weeks post-conception - notably I have developed a 3D culture system which can be used to study human lung development in a dish. My work also includes how immune cells interact with the developing lung using various, cutting edge molecular methods that can look at each cell individually. The period of development after 20 weeks to birth is virtually unexplored and is referred to as the "gap" in the scientific world. In close collaboration with obstetricians and other doctors at UCL, I have designed a way of receiving fresh healthy tissue from any organ from this crucial period of development during the final part of pregnancy. My aims will be 1) to study how the lining of the lung matures, 2) to study how the immune system matures within the lung and also elsewhere in our body, 3) to study how blood vessels mature and how they interact with the lung lining to make a functioning gas exchange unit, allowing oxygen to be transported into the blood compartment and carbon dioxide to be transferred into the air compartment, and finally 4) to set up a late foetal tissue resource for the other research groups working on the maturation of other organs. My overall objective is to study late stage foetal human lung development and maturation, which has the potential for wide-reaching impact on various fields, most notably to improve survival in premature babies and to find ways to reverse the effects of severe lung disease.
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