Study of late-foetal human organ development
Research type
Research Study
Full title
Study of late-foetal human organ development
IRAS ID
253088
Contact name
Marko Nikolic
Contact email
Sponsor organisation
University College London
Clinicaltrials.gov Identifier
Z6364106/2019/10/113, UCL Data Protection Registration number
Duration of Study in the UK
20 years, 0 months, 1 days
Research summary
Knowledge about abnormal organ development is important to understand pathology and to develop novel treatment approaches for individuals with congenital and acquired disease. Most of our current understanding is based on examination of tissues from the embryo and early fetus, collected from women undergoing termination of pregnancy in the first trimester (third) of pregnancy. There is very little known about normal and abnormal organ development from a molecular perspective during the crucial last two-thirds of pregnancy when much remodelling occurs. We aim to collect tissue from different developing organs in the last two-thirds of pregnancy from women who decide to undergo a termination of pregnancy. We believe new knowledge at this stage of pregnancy is fundamental to understand this process and human organ development in general, as it will provide new insights about how organs mature and hence allow the development of novel treatment approaches for the fetus, for premature infants and patients with end-stage organ failure.
One example of an organ in which new information is vitally needed is the lung, where end-stage respiratory failure accounts for the 3rd highest mortality of non-infectious disease death. Currently there is an inability to meet the demands for lung transplantation which itself has only a 5-year survival of 54%, lower than for any other organ. Novel regenerative medicine organ techniques may be able to address the clinical need. Characterising the different stem cell populations in the developing lung and other organs is essential for any future attempt of organ regeneration and repair. We have developed a genetically-modifiable 3D culture system using human embryonic lungs (5-7 week post-conception) which can be used to study human lung development in vitro. However, late fetal lung development is surprisingly under-characterised from a molecular perspective, even though lung immaturity is the major cause of mortality and morbidity associated with prematurity. Using the example of the human lung, the focus of the project will be initially to characterise the various cell types and their interactions in normal human lung. (last two-thirds of pregnancy). A comparison to normal lungs in infancy, childhood and adulthood will be made. The knowledge gained from this will be invaluable to develop new strategies of enhancing organ regeneration and repair as well as ways of improving lung maturity in premature neonates. It will also help us to identify reasons why some babies are affected by developmental and structural problems.
A similar strategy will be taken for other organ systems and tissues. Broadly, tissues and cells will be cultured to study them in the lab, they may undergo implantation into animal models, and examination under the microscope. In addition, we will profile genetic and protein signatures in these tissues and cells.
In summary, a better understanding of both normal and abnormal organ development during pregnancy will bring us a step closer to successful and efficient organ regeneration and repair.
REC name
London - Bromley Research Ethics Committee
REC reference
20/PR/0542
Date of REC Opinion
20 Nov 2020
REC opinion
Further Information Favourable Opinion