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

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.

MicroRNA‑24 attenuates diabetic vascular remodeling by�suppressing the NLRP3/caspase‑1/IL‑1β signaling pathway

“…The current research in this field mainly focuses on improving the function of VSMcs (14)(15)(16)(17)21); however, Ecs have not been extensively investigated. The delay in endothelialization severely compromises the therapeutic effect of Ecs (40). Previously published data by the authors of the current study demonstrated that miR-24 was enriched in VSMcs rather than Ecs (41).…”

CD276 (B7-H3) Maintains Proliferation and Regulates Differentiation in Angiogenic Function in Late Endothelial Progenitor Cells

“…Immunohistochemistry analysis was done as previously reported by our group . Briefly, after paraffin‐embedded sections were cut at 4‐μm sections, the slides were deparaffinized and transferred through progressive ethanol gradients for rehydration.…”

Transplantation of hMSCs Genome Edited with LEF1 Improves Cardio-Protective Effects in Myocardial Infarction

“…Growth factors and cytokines, such as VEGF, insulin-like growth factor (IGF), HGF, interleukin-1b (IL-1b), and IL-6, have been investigated as therapeutic targets in various cell types and diseases. 8,[36][37][38] Recently, these molecules, secreted by MSCs, have been examined in repair and regeneration therapy. 35 We thus investigated the para-crine effect of LEF1/hUCB-MSCs via enhanced secretion of growth factors and cytokines.…”