4.8 Article

Surface-mediated functional gene delivery: An effective strategy for enhancing competitiveness of endothelial cells over smooth muscle cells

Journal

BIOMATERIALS
Volume 34, Issue 13, Pages 3345-3354

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.01.065

Keywords

Endothelial cells; Gene delivery; Hepatocyte growth factor; Layer-by-layer self-assembly; Smooth muscle cells

Funding

  1. National Natural Science Foundation of China [50830106, 21174126, 51103126]
  2. China National Funds for Distinguished Young Scientists [51025312]
  3. National Basic Research Program of China [2011CB606203]
  4. State Key Laboratory of Supramolecular Structure and Materials [SKLSSM201316]
  5. Research Fund for the Doctoral Program of Higher Education of China [20110101110037, 20110101120049]

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The non-biorecognition of general biomaterials and inherent biospecificity of biological systems pose key challenges to the optimal functions of medical devices. In this study, we constructed the surface-mediated functional gene delivery through layer-by-layer self-assembly of protamine sulfate (PrS) and plasmid DNA encoding hepatocyte growth factor (HGF), aiming at specific enhancing endothelial cells (EC) compeititiveness over smooth muscle cells (SMC). Characterizations of the (PrS/HGF-pDNA) multilayered films present the linear buildup with homogeneous and flat topographical feature. The amount of DNA can be easily controlled. By using these multilayered films, both human umbilical vein endothelial cells (HUVEC) and human umbilical artery smooth muscle cells (HUASMC) can be directly transfected when they contact with the multilayered films. On transfection, increasing secretion of HGF has been detected in both HUVEC and HUASMC culture, which leads to selective promotion of HUVEC proliferation. In the co-culture experiment, we also exhibit the promoted and hindered growth of HUVEC and HUASMC, respectively, which could be attributed to the inverse influence of HUVEC on HUASMC. These results collectively demonstrate that our system can be served as a powerful tool for enhancing competitiveness of EC over SMC, which opens perspectives for the regulation of intercellular competitiveness in the field of interventional therapy. (C) 2013 Elsevier Ltd. All rights reserved.

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