Scientists Grow Perfect Human Blood Vessels in a Petri Dish

Diabetic blood vessel changes in patients and human vascular organoids. The basement membrane (green) around the blood vessels (red) is massively enlarged in diabetic patients (white arrows). The human vascular organoids that were made “diabetic” in the laboratory can now be used as diabetic model to identify new treatments.

Credit: IMBA

To tackle this problem, Penninger and his colleagues developed a groundbreaking model: three-dimensional human blood vessel organoids grown in a petri dish. These so-called “vascular organoids” can be cultivated using stem cells in the lab, strikingly mimicking the structure and function of real human blood vessels.

When researchers transplanted the blood vessel organoids into mice, they found that they developed into perfectly functional human blood vessels including arteries and capillaries. The discovery illustrates that it is possible to not only engineer blood vessel organoids from human stem cells in a dish, but also to grow a functional human vascular system in another species.

“What is so exciting about our work is that we were successful in making real human blood vessels out of stem cells,” said Reiner Wimmer, the study’s first author and a postdoctoral research fellow at IMBA. “Our organoids resemble human capillaries to a great extent, even on a molecular level, and we can now use them to study blood vessel diseases directly on human tissue.”

One feature of diabetes is that blood vessels show an abnormal thickening of the basement membrane. As a result, the delivery of oxygen and nutrients to cells and tissues is strongly impaired, causing a multitude of health problems, such as kidney failure, heart attacks, strokes, blindness and peripheral artery disease, leading to amputations.

The researchers then exposed the blood vessel organoids to a “diabetic” environment in a petri dish.

“Surprisingly, we could observe a massive expansion of the basement membrane in the vascular organoids,” said Wimmer. “This typical thickening of the basement membrane is strikingly similar to the vascular damage seen in diabetic patients.”

The researchers then searched for chemical compounds that could block thickening of the blood vessel walls. They found none of the current anti-diabetic medications had any positive effects on these blood vessel defects. However, they discovered that an inhibitor of γ-secretase, a type of enzyme in the body, prevented the thickening of the blood vessel walls, suggesting, at least in animal models, that blocking γ-secretase could be helpful in treating diabetes.

The researchers say the findings could allow them to identify underlying causes of vascular disease, and to potentially develop and test new treatments for patients with diabetes.

Contacts and sources:
Thandi Fletcher
University of British Columbia
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