Generation of human induced pluripotent stem cells (iPSC) for research into common cerebral small vessel disease (cSVD)

Summary

Cerebral Small Vessel Disease or cSVD is a disease affecting the small blood vessels in the brain and it is the most common cause of vascular dementia.

Disease of the small vessel results in disruption of the blood supply, to the deep parts of the brain. This disruption of blood supply stops the surrounding brain cells from working properly, causing them to die over time. As a consequence, people affected by cSVD can develop cognitive impairment, which have a major effect on their quality of life. If the damage is more severe it results in vascular dementia common symptoms of which include mood changes, such as depression, apathy, slowing of thinking and memory loss.

Despite the huge health burden cSVD creates we have little in the way of treatments. One of the main reasons why we don’t have treatments yet is that we don’t fully understand what damages the blood vessels causing cSVD. In addition to well known risk factors, like high blood pressure and diabetes, we know that genetic factors (changes in the DNA) have an important role in stroke. Although new genetic
factors associated with risk of cSVD have been identified, it is not yet clear how these are involved in the causes of cSVD.

To address this, in our laboratory, we have developed a novel model which uses skin cells from volunteers. These skin cells can be transformed into pluripotent stem cells (iPSC) -these are like embryonic stem cells and can turn into any cell type of the body when grown under different conditions. The iPSC are then converted into the cells of the brain blood vessels and create a model of ‘in a dish’.

The purpose of this study is to generate blood vessel cells in the laboratory from volunteers with these genetic variants to help us better understand what causes cSVD by creating a novel ‘blood vessel in a dish’ model which replicates what we see in the brain blood vessels of patients. These models will be also used to identify and evaluate new treatments for cSVD which are crucially needed.