Targeted Gene-and-host Progenitor Cell Therapy for Nonunion Bone Fracture Repair
| Autor: | Ilan Kallai, Yoram Zilberman, Olga Mizrahi, Zulma Gazit, Nadav Kimelman-Bleich, Dan Gazit, Gadi Pelled, Wafa Tawackoli |
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| Rok vydání: | 2011 |
| Předmět: |
Bone Regeneration
Genetic Vectors Population Nonunion Radius bone Mice 03 medical and health sciences 0302 clinical medicine Osteogenesis Drug Discovery Growth Differentiation Factor 2 Genetics medicine Animals Progenitor cell Luciferases Bone regeneration education Molecular Biology 030304 developmental biology Pharmacology Mice Inbred C3H Wound Healing 0303 health sciences education.field_of_study Chemistry Stem Cells Electroporation Gene Transfer Techniques Genetic Therapy Transfection Bone fracture Anatomy medicine.disease Cell biology medicine.anatomical_structure Fractures Ununited 030220 oncology & carcinogenesis Molecular Medicine Female Original Article Collagen Plasmids |
| Zdroj: | Molecular Therapy. 19:53-59 |
| ISSN: | 1525-0016 |
| DOI: | 10.1038/mt.2010.190 |
| Popis: | 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 (µCT) 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. |
| Databáze: | OpenAIRE |
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