Ultrasound-mediated transgene expression in endogenous stem cells recruited to bone injury sites

Galina Shapiro, Ilan Kallai, Dmitriy Sheyn, Wafa Tawackoli, Young Do Koh, Hyun Bae, Tamar Trietel, Riki Goldbart, Joseph Kost, Zulma Gazit, Dan Gazit, Gadi Pelled

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


When fractured, bone can spontaneously heal to a certain extent. In critical-size defects, in which bone loss is severe, a bone graft is required. Faced with the shortcomings of grafts currently in use-autografts, allografts, and mineral-based bone substitutes-efforts are being made to establish new methods of bone regeneration. One promising approach involves the use of exogenous gene-modified mesenchymal stem cells (MSCs), which can rapidly repair large bone defects in animal models. Unfortunately, ex vivo culture of MSCs may add certain complexity to the advancement of this cell therapy to the clinic. Previously, we demonstrated efficient bone regeneration following direct gene delivery to endogenous MSCs that had been attracted to a fracture site. In that study, electroporation was used, but it is an invasive method of gene transfection that may result in tissue damage. Unlike electroporation, sonoporation-the use of ultrasound for gene delivery-is noninvasive, considered safer, and relevant to the clinical setting. In this study, we evaluated the feasibility of ultrasound-based gene delivery to resident MSCs that had been recruited to a fracture site in different animal models. Our results show transient (up to 21days) expression of a reporter gene in radial, vertebral, and tibial bone defects in mice, rats, and a minipig. These results could prove beneficial for the next phase of experiments, in which osteogenic genes such as the bone morphogentic proteins (BMPs) could be utilized to achieve bone regeneration in similar challenging conditions of bone tissue loss.

Original languageEnglish
Pages (from-to)525-531
Number of pages7
JournalPolymers for Advanced Technologies
Issue number5
StatePublished - May 2014


  • Critical-size bone defects
  • Endogenous stem cells
  • Gene delivery
  • Sonoporation


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