Targeted expression of transforming growth factor-β1 in intracardiac grafts promotes vascular endothelial cell DNA synthesis

Young Koh Gou Young Koh, S. J. Kim, M. G. Klug, K. Park, M. H. Soonpaa, L. J. Field

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Intracardiac grafts comprised of genetically modified skeletal myoblasts were assessed for their ability to effect long-term delivery of recombinant transforming growth factor-β (TGF-β) to the heart. C2C12 myoblasts were stably transfected with a construct comprised of an inducible metallothionein promoter fused to a modified TGF-β1 cDNA. When cultured in medium supplemented with zinc sulfate, cells carrying this transgene constitutively secrete active TGF-β1. These genetically modified myoblasts were used to produce intracardiac grafts in syngeneic C3Heb/FeJ hosts. Viable grafts were observed as long as three months after implantation, and immunohistological analyses of mice maintained on water supplemented with zinc sulfate revealed the presence of grafted cells which stably expressed TGF-β1. Regions of apparent neovascularization, as evidenced by tritiated thymidine incorporation into vascular endothelial cells, were observed in the myocardium which bordered grafts expressing TGF-β1. The extent of vascular endothelial cell DNA synthesis could be modulated by altering dietary zinc. Similar effects on the vascular endothelial cells were not seen in mice with grafts comprised of nontransfected cells. This study indicates that genetically modified skeletal myoblast grafts can be used to effect the local, long-term delivery of recombinant molecules to the heart.

Original languageEnglish (US)
Pages (from-to)114-121
Number of pages8
JournalJournal of Clinical Investigation
Volume95
Issue number1
StatePublished - Jan 1 1995

Keywords

  • angiogenesis
  • C2C12 skeletal myoblasts
  • cell transplantation
  • gene therapy
  • intracardiac grafts
  • myocardial repair

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Targeted expression of transforming growth factor-β1 in intracardiac grafts promotes vascular endothelial cell DNA synthesis'. Together they form a unique fingerprint.

  • Cite this