21 January 2019

The circulatory system "in vitro"

Canadian researchers at the University of British Columbia, working under the guidance of Professor Joseph Penninger, managed to grow human blood vessel organoids from pluripotent stem cells in Petri dishes. They are an excellent model for studying the mechanisms of development and developing methods of treatment and prevention of heart diseases, stroke, atherosclerosis, wound healing disorders, as well as vascular disorders associated with diabetes mellitus, Alzheimer's disease, cancer and other pathologies.

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An organoid is a three-dimensional structure grown from stem cells, reproducing an organ in miniature. The vascular organoids grown by the authors consist of endothelial cells and pericytes that spontaneously unite into capillary networks covered with a basement membrane. When transplanted to mice, vascular organoids form a stable perfused vascular tree, including arteries, arterioles and venules.

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Diabetic changes in blood vessels in patients and in human vascular organoids. The basement membrane (green) around the blood vessels (red) is strongly thickened both in patients and in organoids (white arrows).

The authors tested the suitability of their organoids as an experimental model by exposing them to a "diabetic" environment (hyperclycemia and pro-inflammatory cytokines) in a Petri dish. The result was a massive expansion of the basement membrane, a process that fully reflects diabetic vascular damage. In diabetes mellitus, such an abnormal thickening of the basal membrane of blood vessels leads to severe disturbances in the supply of oxygen and nutrients to cells and tissues. As a result, a person develops many health problems, such as kidney failure, myocardial infarction, stroke, blindness and peripheral artery disease leading to amputations.

After that, they searched for chemical compounds that block the thickening of the walls of blood vessels. They did not reveal a positive effect on this process in any of the modern antidiabetic drugs. However, it turned out that the desired effect is exerted by a gamma secretase inhibitor - an enzyme produced in the body. This indicates that blocking the activity of gamma secretase can be used in the treatment of diabetes mellitus.

The researchers hope that the results of their work in the future will help to understand the currently incomprehensible mechanisms of the development of vascular disorders in diabetes mellitus, as well as to develop and test new treatment methods.

Article by Reiner A. Wimmer et al. Human blood vessel organoids as a model of diabetic vasculopathy in the journal Nature.

Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of British Columbia: Scientists grow perfect human blood vessels in a petri dish


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