Autologous transplantation of endothelial progenitor cells genetically modified by adeno-associated viral vector delivering insulin-like growth factor-1 gene after myocardial infarction

Sabyasachi Sen, Juan Merchan, Jarrod Dean, Masaaki Ii, Mary Gavin, Marcy Silver, Tengiz Tkebuchava, Young Sup Yoon, John E.J. Rasko, Ryuichi Aikawa

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The regenerative potential of bone marrow-derived endothelial progenitor cells (EPCs) has been adapted for the treatment of myocardial and limb ischemia via ex vivo expansion. We sought to enhance EPC function by the efficient genetic modification of EPCs in a rat model of myocardial infarction. Peripheral blood EPCs were expanded and transduced, using adeno-associated virus (AAV). AAV-mediated EPC transduction efficacy was 23±1.2%, which was improved by 4.0-to 7.2-fold after pretreatment with the tyrosine kinase inhibitor genistein. Adult rats (n=7 in each group) underwent myocardial infarction by left anterior descending coronary artery occlusion, and received autologous EPCs transduced by AAV-IGF-1 or AAV-lacZ into the periinfarct area. Echocardiography demonstrated that cardiac function in the IGF-1-EPC group was significantly improved compared with the lacZ-EPC control group 12 weeks after myocardial infarction. In addition, IGF-1-expressing EPCs led to reduced cardiac apoptosis, increased cardiomyocyte proliferation, and increased numbers of capillaries in the periinfarct area. AAV expression was limited to the targeted heart region only. Pretreatment with genistein markedly improved AAV transduction of EPCs. IGF-1-expressing EPCs exhibit favorable cell-protective effects with tissue-limited expression in rat heart postinfarction.

Original languageEnglish
Pages (from-to)1327-1334
Number of pages8
JournalHuman Gene Therapy
Volume21
Issue number10
DOIs
Publication statusPublished - 2010 Oct 1

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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