Targeted gene-and-host progenitor cell therapy for nonunion bone fracture repair

Nadav Kimelman-Bleich, Gadi Pelled, Yoram Zilberman, Ilan Kallai, Olga Mizrahi, Wafa Tawackoli, Zulma Gazit, Dan Gazit*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Nonunion fractures present a challenge to orthopedics with no optimal solution. In-vivo DNA electroporation is a gene-delivery technique that can potentially accelerate regenerative processes. We hypothesized that in vivo electroporation of an osteogenic gene in a nonunion radius bone defect site would induce fracture repair. Nonunion fracture was created in the radii of C3H/HeN mice, into which a collagen sponge was placed. To allow for recruitment of host progenitor cells (HPCs) into the implanted sponge, the mice were housed for 10 days before electroporation. Mice were electroporated with either bone morphogenetic protein 9 (BMP-9) plasmid, Luciferase plasmid or injected with BMP-9 plasmid but not electroporated. In vivo bioluminescent imaging indicated that gene expression was localized to the defect site. Microcomputed tomography (νCT) and histological analysis of murine radii electroporated with BMP-9 demonstrated bone formation bridging the bone gap, whereas in the control groups the defect remained unbridged. Population of the implanted collagen sponge by HPCs transfected with the injected plasmid following electroporation was noted. Our data indicate that regeneration of nonunion bone defect can be attained by performing in vivo electroporation with an osteogenic gene combined with recruitment of HPCs. This gene therapy approach may pave the way for regeneration of other skeletal tissues.

Original languageEnglish
Pages (from-to)53-59
Number of pages7
JournalMolecular Therapy
Volume19
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

Fingerprint

Dive into the research topics of 'Targeted gene-and-host progenitor cell therapy for nonunion bone fracture repair'. Together they form a unique fingerprint.

Cite this