Abstract
Atherosclerotic plaques within the vasculature may eventually lead to heart failure. Currently, cardiac stenting is the most effective and least invasive approach to treat this disease. However, in-stent restenosis is a complex chronic side effect of stenting treatment. This study used coronary stents coated with stem cells secreting angiogenic growth factors via an inducible genome-editing system to reduce stent restenosis and induce re-endothelialization within the artery. The characteristics of the cells and their adhesion properties on the stents were confirmed, and the stents were transplanted into a swine model to evaluate restenosis and the potential therapeutic use of stents with stem cells. Restenosis was evaluated using optical coherence tomography (OCT), microcomputed tomography (mCT) and angiography, and re-endothelialization was evaluated by immunostaining after cardiac stent treatment. Compared to a bare metal stent (BMS) or a parental umbilical cord blood-derived mesenchymal stem cell (UCB-MSC)-coated stent, the stents with stem cells capable of the controlled release of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) successfully reduced restenosis within the stent and induced natural re-endothelialization. Furthermore, UCB-MSCs exhibited the ability to differentiate into endothelial cells in Matrigel, and HGF and VEGF improved this differentiation. Our study indicates that stents coated with UCB-MSCs secreting VEGF/HGF reduce the restenosis side effects of cardiac stenting with improved re-endothelialization.
Highlights
Coronary artery disease is an angiocardiopathy that severely impairs health, and it remains the principal cause of mortality worldwide
Cells were seeded on the materials for more than 7 days, and doxycycline (Dox) increased hepatocyte growth factor (HGF)- and vascular endothelial growth factor (VEGF)-secreting umbilical cord blood-derived mesenchymal stem cells (U-Ms) proliferation (Fig. 1b–d)
We confirmed that U-Ms maintained their properties and growth on the stent, and we demonstrated that HGF and VEGF secretion from the engineered stem cells promoted cell proliferation
Summary
Coronary artery disease is an angiocardiopathy that severely impairs health, and it remains the principal cause of mortality worldwide. Coronary stents are a widely used treatment strategy to keep the arteries open. Restenosis and stent thrombosis limit the success of stent treatment. The endothelialization of coronary stents decreases instent restenosis[4,5,6,7]. This process is an important factor in thrombosis prevention and the reduction of vascular smooth muscle cells (VSMCs) proliferation and migration. A coronary stent that is capable of rapid surface endothelialization may become a next-generation stent[7,8,9,10]. We used a very effective combination strategy of gene and cell therapies, in which genome-edited stem cells released proangiogenic growth factors, to improve re-endothelialization
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