Placenta-on-chip to Study Drug Safety in Human Pregnancy
Research type
Research Study
Full title
An Integrated, Physiologically Based, Multiscale Platform to Humanise Preclinical Assessment of Fetal Drug Exposure and Toxicity During Pregnancy
IRAS ID
360020
Contact name
Adeniyi Olagunju
Contact email
Sponsor organisation
University of Liverpool
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
6 years, 5 months, 31 days
Research summary
Pregnancy is a unique window during which the health and wellbeing of future generations are established. To maintain optimal maternal and fetal health, many women require at least one drug during pregnancy. For most drugs, the associated risks are poorly understood because the rodent and rabbit models used during drug development do not recapitulate human physiology. Ongoing research within the Perinatal Pharmacology Group aims to transform the assessment of drug safety during pregnancy by developing a platform to generate human pregnancy-relevant safety information early in drug development.
To achieve this, we will first develop miniature versions of the human placenta on microfluidic chips (placenta-on-chip) by growing placenta cells on small devices that mimic conditions within the body. This 'miniature placentas' will allow us to study the potential impact of drugs taken by a pregnant woman on the placenta, which has been shown to have implications for the developing baby.
Cells for these 'miniature placentas' will be isolated from placenta tissues obtained from Liverpool Women’s Hospital. We will similarly obtain umbilical-cord blood from which we will isolate mesenchymal stem cells for differentiation into placenta cells. Once isolated, both cell types are capable of self-renewal, differentiation and can be cultured to form 'miniature placentas'.
The 'miniature placentas' will be used to investigate: (1) drug-induced perturbations; (2) placenta contribution to drug metabolism and transport. For objective 1, 'miniature placentas' will be exposed to drugs used in validating new alternative methods for embryofetal development toxicity. These are drugs known to be associated with poor pregnancy and fetal outcomes in the absence of maternal toxicity (positive control), and those with well-established safety profile in human pregnancy (negative control). RNA and protein will be isolated for transcriptomics, epigenetics analyses, and proteomics. Integrated analysis of multi-omics data will be used to uncover molecular signatures of drug-induced perturbations in human placenta.
REC name
North East - York Research Ethics Committee
REC reference
25/NE/0119
Date of REC Opinion
19 Jun 2025
REC opinion
Favourable Opinion