Evaluation of in vivo endothelialization of VEGF coated stents with allogeneic mesenchymal stem cells
Date
2020-07-15
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Deploying bare metal stents in the brain is a widely used procedure to repair damaged blood vessels for pathologies including aneurysms, vessel dissections and atherosclerosis. However, the major complication of this procedure is a stroke, which can occur in up to 11% of cases. The cause of the stroke is typically due to platelet interactions with the foreign material leading to blood clot formation also known as in-stent thrombosis. Current standard of care intracranial stents are significantly thrombogenic and require patients to remain on lifelong antiplatelet medications, which can lead to other health complications and be a financial burden for both the patient and the healthcare system. A possibility to mitigate in-stent thrombosis is the rapid formation of a new inner lining of the stent through the process of endothelialization, which conceals the foreign material from platelets. To promote rapid endothelialization, mesenchymal stem cells (MSCs) are a promising cell type. MSCs are a type of multipotent stem cell that have the capability to differentiate into cells lining the blood vessel wall or produce cytokines that can lead to endothelial formation. MSCs are naturally found in small numbers in the circulating blood of mammals, and previous research has suggested that the presence of vascular endothelial growth factor (VEGF) can augment the vasculogenic and angiogenic capabilities of MSCs. In this thesis, we developed biologically modified stents with VEGF coatings to recruit exogenously administered MSCs and compared them to several control groups, including bare metal stents which are currently in clinical use. In vitro experiments were used to determine translatability of the stent coating technique to in vivo trials, and animal studies were performed to evaluate our innovative method in terms of neointima formation and thrombus burden. Our results demonstrated that the protein coating made up of VEGF and PLGA (poly lactic-co-glycolic acid) is significantly retained after catheter delivery, and MSCs may be attracted to the coating. We also showed that VEGF and MSCs, VEGF alone and that MSCs alone significantly improve endothelialization but do not necessarily deter thrombus formation compared to uncoated controls. These studies can potentially solve a major problem associated with vascular stent implantation and provide the initial translational work needed for commercialization
Description
Keywords
Stent, VEGF, Mesenchymal stem cells, Endothelialization, Thrombus, Neointima, Aneurysm, Intracranial
Citation
Panchendrabose, K. (2020). Evaluation of in vivo endothelialization of VEGF coated stents with allogeneic mesenchymal stem cells (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.