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

J Cell Biochem. 2017 Nov;118(11):3627-3634. doi: 10.1002/jcb.26220. Epub 2017 Jul 31.

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. © 2017 Wiley Periodicals, Inc.

Keywords: BIOMATERIAL; BONE FORMATION; CELL THERAPY; DELIVERY SYSTEM; IN VIVO; INDUCIBLE SUICIDE GENE.

MeSH terms

  • Adenoviridae*
  • Animals
  • Bone Morphogenetic Protein 2* / biosynthesis
  • Bone Morphogenetic Protein 2* / genetics
  • Cell- and Tissue-Based Therapy / methods*
  • Female
  • Genetic Therapy / methods*
  • Humans
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Osteogenesis*
  • Spinal Fusion / methods*
  • Transduction, Genetic*

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2