MSC-based VEGF gene therapy in rat myocardial infarction model using facial amphipathic bile acid-conjugated polyethyleneimine

Hyung Ho Moon, Min Kyung Joo, Hyejung Mok, Minhyung Lee, Ki Chul Hwang, Sung Wan Kim, Ji Hoon Jeong, Donghoon Choi, Sun Hwa Kim

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

Abstract

Mesenchymal stem cells (MSCs) have attracted much attention in regenerative medicine owing to their apparent usefulness as multi-potent replacement cells. The potential of MSC therapy can be further improved by transforming MSCs with therapeutic genes that maximize the efficacy of gene therapy and their own therapeutic ability. Since most conventional transfection methodologies have shown marginal success in delivering exogenous genes into primary cultured cells, efficient gene transfer into primary MSCs is a prerequisite for the development of MSC-based gene therapy strategies to achieve repair and regeneration of damaged tissues. Herein, facially amphipathic bile acid-modified polyethyleneimine (BA-PEI) conjugates were synthesized and used to transfer hypoxia-inducible vascular endothelial growth factor gene (pHI-VEGF) in MSCs for the treatment of rat myocardial infarction. Under the optimized transfection conditions, the BA-PEI conjugates significantly increased the VEGF protein expression levels in rat MSCs, compared with traditional transfection methods such as Lipofectamine™ and branched-PEI (25kDa). Furthermore, the prepared pHI-VEGF-engineered MSCs (VEGF-MSCs) resulted in improved cell viability, particularly during severe hypoxic exposure invitro. The transplantation of MSCs genetically modified to overexpress VEGF by BA-PEI enhanced the capillary formation in the infarction region and eventually attenuated left ventricular remodeling after myocardial infarction in rats. This study demonstrates the applicability of the BA-PEI conjugates for the efficient transfection of therapeutic genes into MSCs and the feasibility of using the genetically engineered MSCs in regenerative medicine for myocardial infarction.

Original languageEnglish
Pages (from-to)1744-1754
Number of pages11
JournalBiomaterials
Volume35
Issue number5
DOIs
Publication statusPublished - 2014 Feb

Bibliographical note

Funding Information:
This work was supported by grants from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2010-0022471 ), Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea ( A110879 ) and the Intramural Research Program of KIST.

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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