New Blood Vessel Model Leads to Progeria Insights

Biomedical engineers at Duke University constructed an advanced disease model for blood vessels prompting insights into Hutchinson-Gilford progeria syndrome (HGPS), according to a study published in Stem Cell Reports.

HGPS is an extremely rare genetic disease that is caused by a random mutation in the Lamin A gene (LMNA), which produces a form of the protein progerin. The disease manifests in children as a variety of symptoms resembling accelerated aging. Due to nuclear accumulation of the progerin protein, patients develop weakened blood vessels and atherosclerosis. Most die of a heart attack or stroke during their teenage years.

The new disease model enabled the researchers to determine the unique role of the endothelium, the inner lining of blood vessels, in progeria. The model was derived from patients’ stem cells, and for the first time, the researchers were able to grow layers of blood vessels, including both the smooth muscle and the endothelium.

“Combined with an advanced experimental setup that pushes culture media that models blood through the engineered blood vessels, the model reveals that the endothelium responds differently to flow and shear stress with progeria than it does when healthy,” according to a press release.

The researchers were able to use stem cells taken from patients’ skin to compare diseased endothelium, which produced symptoms of progeria, to controls.

Because there are only around 250 people living with the disease in the world, it is difficult to study the vasculature of these patients to determine the cause or cell types responsible for atherosclerosis. Clinical trials are difficult to conduct, and researchers hope this new model can be used to test out treatments for the disease.

The “improved induced pluripotent stem cell-derived tissue-engineered blood vessels provides a more sensitive platform that allows for better evaluation of differences in the HGPS disease state at not only the 2D level, but the 3D tissue level as well,” the researchers said.

The exact mechanism behind this observation is still unclear, and future studies are needed to further specify the cause of HGPS. However, the researchers feel “this work indicates that the endothelium may play a role in atherosclerotic development in HGPS and emphasizes the need to further evaluate the role of these cells in this complex disease state.”

Reference

Atchison L, Abutaleb NO, Snyder-Mounts E, et al. iPSC-derived endothelial cells affect vascular function in a tissue-engineered blood vessel model of Hutchinson-Gilford progeria syndrome [published online February 6, 2020]. Stem Cell Reports. doi: 10.1016/j.stemcr.2020.01.005.