Inhibitory effects of mesenchymal stem cells in intimal hyperplasia after balloon angioplasty

J Vasc Surg. 2016 Feb;63(2):510-7. doi: 10.1016/j.jvs.2014.08.058. Epub 2014 Sep 18.

Abstract

Objective: Intimal hyperplasia is a major cause of restenosis after arterial bypass and balloon angioplasty. Induction of rapid re-endothelialization has been proposed to reduce intimal hyperplasia. The aim of this study was to evaluate the inhibitory effect of mesenchymal stem cells on intimal hyperplasia.

Methods: Male New Zealand white rabbits were fed 1% cholesterol diets from 1 week before balloon angioplasty to the day of harvest. After dissection of rabbit carotid arteries, balloon angioplasty was performed with a 2F Fogarty embolectomy catheter. The injured carotid artery was coated with a mixture of 7 × 10(6) human umbilical cord mesenchymal stem cells (HUC-MSCs) and fibrin matrix. The carotid arteries were harvested 2, 4, and 8 weeks thereafter, and immunofluorescent staining and quantitative real-time polymerase chain reaction analysis were performed.

Results: The intima/media ratio was significantly reduced in the group treated with HUC-MSCs compared with the nontreated group (Student t-tests, *P < .05). The area of re-endothelialization was significantly higher (Student t-tests, *P < .05) in the group treated with HUC-MSCs than in the nontreated group. Expression of angiogenic genes such as vascular endothelial growth factor, platelet-derived growth factor, kinase insert domain receptor 1, angiopoietin 1, and angio-associated migratory cell protein was increased (analysis of variance, P < .05) in the group treated with HUC-MSCs relative to the nontreated group.

Conclusions: Our study showed that HUC-MSCs reduce the formation of intimal hyperplasia through rapid re-endothelialization. This result might be applied to development of stem cell-coated stents as well as to development of a stem cell-containing sheet coat for inhibition of intimal hyperplasia after angioplasty or surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenic Proteins / genetics
  • Angiogenic Proteins / metabolism
  • Angioplasty, Balloon*
  • Animals
  • Carotid Arteries / metabolism
  • Carotid Arteries / pathology*
  • Carotid Artery Injuries / etiology
  • Carotid Artery Injuries / genetics
  • Carotid Artery Injuries / metabolism
  • Carotid Artery Injuries / pathology
  • Carotid Artery Injuries / surgery*
  • Diet, High-Fat
  • Disease Models, Animal
  • Gene Expression Regulation
  • Humans
  • Hyperplasia
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Neointima*
  • Rabbits
  • Re-Epithelialization
  • Time Factors
  • Vascular Remodeling

Substances

  • Angiogenic Proteins