Researchers have developed a new exosome-coated shunt that enhances tissue repair and heals vascular injury without narrowing the blood vessel, while also providing regenerative stem cell-derived therapy to ischaemic (blood starved) tissue.
A metal stent is often used in angioplasty to reinforce arterial walls and prevent collapse once the blockage is removed. However, placing the stent usually injures the blood vessel wall, stimulating smooth muscle cells to proliferate and migrate to the site to repair the injury. What results is restenosis, a re-narrowing of the blood vessel previously opened by angioplasty.
“The inflammatory response that stents cause can decrease their benefit,” said corresponding author Ke Cheng. “Ideally, if we could stop smooth muscle cells from over-reacting and proliferating, but recruit endothelial cells to cover the stent, it would mitigate the inflammatory response and prevent restenosis.” Cheng is the Randall B. Terry Jr. Distinguished Professor in Regenerative Medicine at NC State and a professor in the NC State/UNC-Chapel Hill Joint Department of Biomedical Engineering.
There are drug-eluting stents currently in use coated with drugs that ihibit cell proliferation, but these anti-proliferative drugs also delay the desired outcome of endothelial cells covering the stent.
To solve this, Prof Cheng and his team developed a stent coating made up of exosomes derived from mesenchymal stem cells. Exosomes are tiny nano-sized sacs secreted by most cell types. As the exosome surfaces are similar to cell membranes, they ‘camouflage’ the stent to fool smooth muscle cells and the body’s immune system. The exosomes also encourage endothelial cells to cover the stent and, in the case of injury, travel downstream to the site to promote tissue repair.
In order to prevent the therapy running out early, the stent releases exosomes when it encounters reactive oxygen species (ROS) – which are more prevalent during an inflammatory response.
“Think of it as a smart release function for the exosomes,” Cheng says. “Ischemic reperfusion injuries, which occur when blood flow is diminished and then reestablished, create a lot of ROS. Let’s say the heart is damaged by ischemia. The enhanced ROS will trigger the release of the exosomes on the stent, and regenerative therapy will travel through the blood vessel to the site of the injury.”
Using in vitro testing, they found that in the presence of ROS, the exosomes released up to 60% of their secretions within 48 hours after the injury.
The researchers used a rat model of ischaemic injury to compare their exosome-eluting stent (EES) to both a bare metal stent (BMS) and a drug-eluting stent (DES). They found that in comparison to the BMS, their stent performed better in both reducing stenosis and stimulating 0endothelial coverage.
While the DES and EES were similar in preventing restenosis, the EES caused lesser vessel wall injury and had better endothelial coverage overall. Additionally, the exosomes released from EES promoted muscle regeneration in rats with hind limb ischaemia. Next, the researchers plan testing of the system in a larger animal model, eventually leading to clinical trials.
“This bioactive stent promotes vascular healing and ischaemic repair, and a patient wouldn’t need additional procedures for regenerative therapy after the stent is in place. The stent is the perfect carrier for exosomes, and the exosomes make the stent safer and more potent in tissue repair,” said Prof Cheng.
Source: News-Medical.Net
Journal information: Hu, S., et al. (2021) Reopen and Regenerate: Exosome-Coated Stent Heals Vascular Injury, Repairs Damaged Tissue. Nature Biomedical Engineering. doi.org/10.1038/s41551-021-00705-0.
