Exogenously regulated stem cell-mediated gene therapy for bone regeneration

Ioannis K. Moutsatsos, Gadi Turgeman, Shuanhu Zhou, Basan Gowda Kurkalli, Gadi Pelled, Liat Tzur, Pamela Kelley, Natalie Stumm, Sha Mi, Ralph Müller, Yoram Zilberman, Dan Gazit

Research output: Contribution to journalArticlepeer-review

245 Scopus citations


Regulated expression of transgene production and function is of great importance for gene therapy. Such regulation can potentially be used to monitor and control complex biological processes. We report here a regulated stem cell-based system for controlling bone regeneration, utilizing genetically engineered mesenchymal stem cells (MSCs) harboring a tetracycline-regulated expression vector encoding the osteogenic growth factor human BMP-2. We show that doxycycline (a tetracycline analogue) is able to control hBMP-2 expression and thus control MSC osteogenic differentiation both in vitro and in vivo. Following in vivo transplantation of genetically engineered MSCs, doxycycline administration controlled both bone formation and bone regeneration. Moreover, our findings showed increased angiogenesis accompanied by bone formation whenever genetically engineered MSCs were induced to express hBMP-2 in vivo. Thus, our results demonstrate that regulated gene expression in mesenchymal stem cells can be used as a means to control bone healing.

Original languageEnglish
Pages (from-to)449-461
Number of pages13
JournalMolecular Therapy
Issue number4
StatePublished - 2001
Externally publishedYes


  • Bone morphogenetic protein-2
  • Bone regeneration
  • Fracture healing
  • Gene expression
  • Gene therapy
  • Tetracycline regulation


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