Development of a Cell-Based Gene Therapy Approach to Selectively Turn Off Bone Formation

Pedro Alvarez-Urena, Banghe Zhu, Gabrielle Henslee, Corinne Sonnet, Eleanor Davis, Eva Sevick-Muraca, Alan Davis, Elizabeth Olmsted-Davis

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Cell and gene therapy approaches are safer when they possess a system that enables the therapy to be rapidly halted. Human mesenchymal stem cells were transduced with an adenoviral vector containing the cDNA for bone morphogenetic protein 2 (AdBMP2) to induce bone formation. To make this method safer, a system to quickly kill these virally transduced cells was designed and evaluated. Cells were encapsulated inside poly(ethylene glycol) diacrylate (PEG-Da) hydrogels that are able to shield the cells from immunological destruction. The system involves an inducible caspase-9 (iCasp9) activated using a specific chemical inducer of dimerization (CID). Delivering AdBMP2-transduced human mesenchymal stem cells encapsulated in PEG-Da hydrogel promoted ectopic ossification in vivo, and the iCasp9 system allowed direct control of the timing of apoptosis of the injected cells. The iCasp9-CID system enhances the safety of delivering AdBMP2-transduced cells, making it a more compelling therapeutic for bone repair and spine fusion. J. Cell. Biochem. 118: 3627–3634, 2017.

Original languageEnglish (US)
Pages (from-to)3627-3634
Number of pages8
JournalJournal of Cellular Biochemistry
Volume118
Issue number11
DOIs
StatePublished - Nov 2017

Keywords

  • BIOMATERIAL
  • BONE FORMATION
  • CELL THERAPY
  • DELIVERY SYSTEM
  • IN VIVO
  • INDUCIBLE SUICIDE GENE

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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