Engineering functional BMP-2 expressing teratoma-derived fibroblasts for enhancing osteogenesis.
Yoon Young GoJi Yeon MunSung-Won ChaeShin Hye KimHoseok SongJae Jun SongPublished in: Scientific reports (2018)
Bone morphogenetic protein 2 (BMP-2) is considered an effective growth factor for bone formation, and is used for making osteo-inductive scaffolds, but the related clinical investigations have shown low success rates. In this study, we genetically manipulated teratoma-derived fibroblast (TDF) cells by simultaneous introduction of BMP-2 and herpes simplex virus-thymidine kinase (HSV-tk) encoding genes. Self-production of BMP-2 in TDF cells strongly enhanced the alkaline phosphatase (ALP) activity, calcium content, and elevated the mRNA expression of osteogenic marker genes during in vitro osteogenesis. The bone formation volume was also remarkably enhanced in calvarial and femoral critical-size defect models. Ganciclovir (GCV) treatment induced apoptosis in TDF cells co-expressing HSV-tk and BMP-2, implying that HSV-tk suicide gene can modulate the side-effects of stem cell therapy, e.g., development of uncontrollable teratoma and tumor formation. Altogether, our findings revealed a safe and highly efficient technique with potential therapeutic applications for bone regeneration.
Keyphrases
- bone regeneration
- induced apoptosis
- mesenchymal stem cells
- endoplasmic reticulum stress
- herpes simplex virus
- signaling pathway
- cell therapy
- oxidative stress
- growth factor
- highly efficient
- cell cycle arrest
- genome wide
- stem cells
- bone marrow
- genome wide identification
- dna methylation
- transcription factor
- single cell
- tyrosine kinase
- copy number