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1. Coronary stents with inducible VEGF/HGF-secreting UCB-MSCs reduced restenosis and increased re-endothelialization in a swine model

Author

Hyun-Kyung Chang, Pyung-Hwan Kim, Dong Wook Kim, Hyun-Min Cho, Mi Jin Jeong, Dea Han Kim, Yoon Ki Joung, Kyung Seob Lim, Han Byul Kim, Han Cheol Lim, Dong Keun Han, Young Joon Hong, and Je-Yoel Cho

Subjects
Medicine, Biochemistry, QD415-436
Abstract

Heart disease: Coated stents reduce repeated blocking of arteries Coating stents with modified stem cells may reduce the risk of repeated artery blocking in the treatment of heart disease. Currently, tubular stents are used to re-open arteries narrowed or blocked by the build-up of fatty deposits. However, if the artery is damaged by the stent or tries to reject it, the resulting inflammatory immune response can result in restenosis, or re-blocking. Je-Yoel Cho at Seoul National University, Republic of Korea, and co-workers trialed stents coated with modified stem cells in swine models. The stem cells are designed to secrete controlled levels of two growth factors, enabling them to differentiate into blood vessel lining cells and build a protective layer around the stent. In comparison with standard stents and stents coated with unmodified stem cells, the modified stents improved blood flow and reduced restenosis.

Published
2018
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2. Coronary stents with inducible VEGF/HGF-secreting UCB-MSCs reduced restenosis and increased re-endothelialization in a swine model

Author

Je-Yoel Cho, Yoon Ki Joung, Young Joon Hong, Hyunmin Cho, Dong Keun Han, Dong Wook Kim, Han Cheol Lim, Hyun-Kyung Chang, Mi Jin Jeong, Pyung-Hwan Kim, Dea Han Kim, Han Byul Kim, and Kyung Seob Lim

Subjects
Vascular Endothelial Growth Factor A, 0301 basic medicine, Bare-metal stent, Pathology, Carcinogenesis, Swine, medicine.medical_treatment, Clinical Biochemistry, lcsh:Medicine, 030204 cardiovascular system & hematology, Biochemistry, chemistry.chemical_compound, 0302 clinical medicine, Restenosis, Medicine, lcsh:QD415-436, Mice, Inbred BALB C, Hepatocyte Growth Factor, Fetal Blood, Coronary Vessels, Vascular endothelial growth factor, surgical procedures, operative, Molecular Medicine, Stents, Hepatocyte growth factor, Stem cell, medicine.drug, medicine.medical_specialty, Mice, Nude, Neovascularization, Physiologic, Mesenchymal Stem Cell Transplantation, lcsh:Biochemistry, Coronary Restenosis, 03 medical and health sciences, Animals, Humans, cardiovascular diseases, Molecular Biology, Cell Proliferation, Matrigel, business.industry, lcsh:R, Mesenchymal stem cell, Stent, Mesenchymal Stem Cells, equipment and supplies, medicine.disease, Disease Models, Animal, 030104 developmental biology, chemistry, Endothelium, Vascular, business, Biomarkers
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.

Published
2018

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