Understanding vascular complications in diabetes using in vitro models
Research type
Research Study
Full title
Identifying the cellular and molecular mechanisms that underpin vascular complications in diabetes using in vitro vascular models.
IRAS ID
327328
Contact name
Fiona Wilkinson
Contact email
Sponsor organisation
Manchester Metropolitan University
Clinicaltrials.gov Identifier
55562, University Internal ethics no. (Ethos)
Duration of Study in the UK
4 years, 11 months, 28 days
Research summary
The prevalence of type 2 diabetes mellitus(T2DM) is increasing and generates a high-cost burden in the treatment of associated co-morbidities. Despite glycaemic(sugar), blood pressure and lipid modification therapies (eg statins), vascular complications increase cardiovascular disease(CVD) risk by 4-fold. The diabetic environment promotes fatty tissue build up in the arteries (atherosclerosis) and blood clotting events via a number of interlinked cell and molecular pathways including activation of the delicate lining of the blood vessel (endothelial cell), inflammation, oxidative stress, leading to poor vascular function where the blood vessels become stiff and potentially calcified losing their ability to contract and relax. Furthermore, dysregulation of the immune system makes T2DM patients more susceptible to fungal infections which are associated with vascular damage and increased mortality.
Research studies have primarily focused on understanding the behaviour of blood and blood vessel wall cells in isolated cell culture conditions. Whilst this is useful, they do not represent the 3-dimensional architecture of the vessel wall nor the communication between cells. Therefore, it is important to develop co-culture models to understand whether cell communication is different in diseases like T2D. Our previous work has demonstrated the importance of utilising cells isolated from patient blood and discarded tissue to replicate the disease state more closely in laboratory models.
This is a laboratory-based, basic science study to generate complex cell models using human cells isolated from blood and discarded tissue that recapitulate a healthy control (no T2D) versus a T2D environment. We will use these models to establish the underlying disease mechanism that occur in vascular cells (eg endothelial cells, vascular smooth muscle cells) and blood cells, (eg neutrophils and platelets) in T2D, that may lead to the identification of novel drugs treat vascular disease. We can also use this model system to test potential therapies for vascular disease.REC name
Yorkshire & The Humber - Leeds West Research Ethics Committee
REC reference
24/YH/0089
Date of REC Opinion
2 Jul 2024
REC opinion
Further Information Favourable Opinion