Researchers Develop Breakthrough Model of Thoracic Aortic Aneurysm in Rats

Researchers at Michigan Medicine have successfully created a functional model of thoracic aortic aneurysm using human cells in laboratory rats, paving the way for a better understanding of the potentially fatal condition and the development of more effective treatments. The breakthrough model, developed by Dr. Bo Yang and his team, uses bioengineered vascular grafts to mimic the condition, allowing for the testing of potential drugs and screening methods to prevent deadly aortic dissections or ruptures. This description focuses on the primary topic of the article (thoracic aortic aneurysm model), the main entities involved (researchers at Michigan Medicine, Dr. Bo Yang, and his team), the context (laboratory setting), and the significant actions and implications (development of a functional model, potential for better understanding and treatment). The description also provides objective and relevant details that will help an AI generate an accurate visual representation of the article's content, such as the use of bioengineered vascular grafts and laboratory rats.

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Bijay Laxmi
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Researchers Develop Breakthrough Model of Thoracic Aortic Aneurysm in Rats

Researchers Develop Breakthrough Model of Thoracic Aortic Aneurysm in Rats

Researchers at Michigan Medicine have successfully created a functional model of thoracic aortic aneurysm using human cells in laboratory rats. This breakthrough paves the way for a better understanding of the potentially fatal condition and the development of more effective treatments. Thoracic aortic aneurysm, characterized by a weakening and bulging of the body's largest blood vessel in the chest, currently has no medical treatments and often requires open-heart surgery.

Why this matters: This breakthrough has significant implications for the treatment of thoracic aortic aneurysm, a condition that affects thousands of people worldwide and can be fatal if left untreated. The development of effective treatments could save countless lives and improve the quality of life for those affected by this condition.

The research team, led by Dr. Bo Yang, a cardiac surgeon and basic scientist, used bioengineered vascular grafts (BVGs) to create the model. They extracted cells from patients with a pathogenic variant that leads to aortic aneurysm, reprogrammed them into induced pluripotent stem cells, and differentiated them into smooth muscle cells. The smooth muscle cells were then seeded onto a biodegradable scaffold, which formed stable, self-supporting grafts over eight weeks.

To test the viability of the aneurysm model, the researchers used CRISPR-Cas9 gene editing to introduce the pathogenic variant in normal human cells and correct the variant in patient cells. The control and experimental BVGs were implanted into the carotid arteries of rats. The results showed that the bioengineered grafts carrying the aneurysm variant had impaired mechanical properties and dilated compared to the healthy grafts. The genetically modified graft grew up to around 40%, resembling human formation of thoracic aortic aneurysm.

"We now have the first efficient 3D model of this disease using human cells," said Dr. Bo Yang. "This opens a new avenue for drug development and more effective screening to one day stop the aneurysm before a deadly aortic dissection or rupture." The researchers are currently exploring potential drugs that could be tested using their new model.

The model provides a platform to study the pathogenesis of Loeys-Dietz Syndrome and other pathogenic variants associated with thoracic aortic aneurysm and dissection. "This is a major first step. We have a model that is human cell-based, which puts us in a position to more effectively assess drugs aimed to treat the condition," said Dr. Dogukan Mizrak, co-senior author of the study.

Thoracic aortic aneurysm affects approximately 6-10 people per 100,000 and caused over 9,000 deaths in the United States in 2019. The study, supported by the National Institutes of Health and the American Heart Association Postdoctoral Fellowship, represents a significant advancement in understanding and potentially treating this life-threatening condition. "This is an incredibly exciting time for research in the area of aortic aneurysm," said Dr. Eugene Chen, co-senior author of the study.

Key Takeaways

  • Researchers create functional model of thoracic aortic aneurysm using human cells in lab rats.
  • Breakthrough paves way for better understanding and development of effective treatments.
  • Model uses bioengineered vascular grafts with patient cells to mimic aneurysm formation.
  • Researchers can now test potential drugs and screen for effective treatments.
  • Study represents significant advancement in understanding and treating life-threatening condition.