Offers new hope for persons living with diabetes
By Sola Ogundipe
In what has been described as the world’s first, scientists have managed to grow perfect human blood vessels as organoids in a petri dish in the laboratory. An organoid is a three-dimensional structure grown from stem cells that mimics an organ and can be used to study aspects of that organ in a petri dish.
The findings could allow identification of underlying causes of diabetes and to potentially develop and test new treatments for the disease.
The breakthrough engineering technology advances research into a key pathway to potentially prevent changes to blood vessels which is a major cause of death and morbidity among persons living with diabetes.
According to the International Diabetes Foundation, diabetes affects an estimated 425 million people worldwide, and more than 16 million people in the Afro Region; by 2045 it will be around 41 million. There were 1.7 million cases of diabetes in Nigeria in 2015.
Senior author of the study, Josef Penninger, who is the Canada 150 Research Chair in Functional Genetics, noted that being able to build human blood vessels as organoids from stem cells is a game changer.
Penninger, who is Director of the Life Sciences Institute at UBC and founding director of the Institute for Molecular Biotechnology of the Austrian Academy of Sciences, IMBA, said: “Every single organ in our body is linked with the circulatory system. This could potentially allow researchers to unravel the causes and treatments for a variety of vascular diseases, from Alzheimer’s disease, cardiovascular diseases, wound healing problems, stroke, cancer and, of course, diabetes.”
Many diabetic symptoms are the result of changes in blood vessels that result in impaired blood circulation and oxygen supply of tissues. Despite its prevalence, very little is known about the vascular changes arising from diabetes. This limitation has slowed the development of much-needed treatment.
Often, there are no symptoms for diabetes, but when symptoms do occur, they include excessive thirst or urination, fatigue, weight loss or blurred vision.
To tackle the 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 they 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, 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 found none of the current anti-diabetic medications had any positive effects on these blood vessel defects. However, they discovered that an inhibitor of secretase, a type of enzyme in the body, prevented the thickening of the blood vessel walls, suggesting, at least in animal models, that blocking secretase could be helpful in treating diabetes.