Induction of reparative dentin formation by ultrasound-mediated gene delivery of Growth/differentiation factor 11

Misako Nakashima, Katsuro Tachibana, Koichiro Iohara, Masataka Ito, Masaki Ishikawa, Akifumi Akamine

Research output: Contribution to journalArticlepeer-review

90 Citations (Scopus)

Abstract

Bone morphogenetic proteins (BMPs) are morphogens implicated in embryonic and regenerative odontogenic differentiation. Gene therapy has the potential to induce reparative dentin formation for potential pulp capping. We have optimized the gene transfer of Growth/differentiation factor 11 (Gdf11)/Bmp11 plasmid DNA into dental pulp stem cells by sonoporation in viva. Dental pulp tissue treated with plasmid pEGFP or CMV-LacZ in 5-10% Optison (Molecular Biosystems Inc., San Diego, CA) and stimulated by ultrasound (1 MHz, 0.5 W/cm2, 30 sec) showed significant efficiency of gene transfer and high level of protein production selectively in the local region, within 500 μm of the amputated site of the pulp tissue. The Gdf11 cDNA plasmid transferred into dental pulp tissue by sonoporation in vitro, induced the expression of dentin sialoprotein (Dsp), a differentiation marker for odontoblasts. The transfection of Gdf11 by sonoporation stimulated a large amount of reparative dentin formation on the amputated dental pulp in canine teeth in viva. These results suggest the possible use of BMPs using ultrasound-mediated gene therapy for endodontic dental treatment.

Original languageEnglish
Pages (from-to)591-597
Number of pages7
JournalHuman Gene Therapy
Volume14
Issue number6
DOIs
Publication statusPublished - 2003 Apr 10
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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