Lab-grown blood vessels are shedding fresh light on how damage to the brain’s small vessels can cause them to leak, contributing to dementia and stroke.
Even better, this study discovered a therapeutic target that could block these leaks and perhaps lower a person’s chance of brain-damaging blood vessel leaks.
Antibiotics and anti-cancer medications that block a type of molecule called metalloproteinases (MMPs) repaired damage and prevented leaks in lab-grown blood arteries.
“These particular drugs come with potentially significant side effects, so wouldn’t in themselves be viable to treat small vessel disease,” said study author Dr. Alessandra Granata, of the department of clinical neurosciences at the University of Cambridge in England.
“But they show that in theory, targeting MMPs could stop the disease,” Granata added in a university news release. “Our model could be scaled up relatively easily to test the viability of future potential drugs.”
According to the researchers’ background notes, cerebral small vascular disease (SVD) accounts for nearly half (45%) of dementia cases worldwide.
It is also responsible for approximately one in every five (20%) ischemic strokes, which occur when a blood clot prevents blood flow to the brain. The majority of cases are related with chronic conditions such as high blood pressure and type 2 diabetes, and they mainly afflict persons in their forties and fifties.
Cambridge researchers collected cells from skin biopsies of individuals with a rare genetic form of small artery disease caused by a mutation in the COL4 gene for this investigation.
The researchers reprogrammed the skin cells to become stem cells, which can evolve into practically any form of cell in the body.
“Despite the number of people affected worldwide by small vessel disease, we have little in the way of treatments because we don’t fully understand what damages the blood vessels and causes the disease,” Granata explained.
“Most of what we know about the underlying causes tends to come from animal studies, but they are limited in what they can tell us,” she noted. “That’s why we turned to stem cells to generate cells of the brain blood vessels and create a disease model ‘in a dish’ that mimics what we see in patients.”
The blood arteries in the brain are constructed around a scaffolding called an extracellular matrix, which coats and supports the small vessels. This matrix’s health is dependent on the COL4 gene.
Researchers discovered that disrupting this matrix causes small blood vessels to bleed.
MMPs were also discovered as being important in this damage by the researchers. MMPs are normally important for matrix maintenance, but producing too many might harm the structure.