Engineering functional BMP-2 expressing teratoma-derived fibroblasts for enhancing osteogenesis

Yoon Young Go, Ji Yeon Mun, Sungwon Chae, Shin Hye Kim, Hoseok Song, Jae-Jun Song

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article number14581
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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Bone Morphogenetic Protein 2
Teratoma
Osteogenesis
Thymidine Kinase
Simplexvirus
Fibroblasts
Genes
Ganciclovir
Bone Regeneration
Cell- and Tissue-Based Therapy
Thigh
Suicide
Alkaline Phosphatase
Intercellular Signaling Peptides and Proteins
Stem Cells
Apoptosis
Calcium
Messenger RNA
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • General

Cite this

Engineering functional BMP-2 expressing teratoma-derived fibroblasts for enhancing osteogenesis. / Go, Yoon Young; Mun, Ji Yeon; Chae, Sungwon; Kim, Shin Hye; Song, Hoseok; Song, Jae-Jun.

In: Scientific Reports, Vol. 8, No. 1, 14581, 01.12.2018.

Research output: Contribution to journalArticle

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AU - Song, Jae-Jun

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