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

作者：Alvarez Urena Pedro; Zhu Banghe; Henslee Gabrielle; Sonnet Corinne; Davis Eleanor; Sevick Muraca Eva; Davis Alan; Olmsted Davis Elizabeth^*

来源：Journal of Cellular Biochemistry, 2017, 118(11): 3627-3634.

DOI：10.1002/jcb.26220

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

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.

• 出版日期2017-11