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Repairing critical-sized calvarial defects with BMSCs modified by a constitutively active form of hypoxia-inducible factor-1α and a phosphate cement scaffold
- Source :
- Biomaterials. 32:9707-9718
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- Tissue engineering combined with gene therapy represents a promising approach for bone regeneration. The Hypoxia-inducible factor-1α (HIF-1α) gene is a pivotal regulator of vascular reactivity and angiogenesis. Our recent study has showed that HIF-1α could promote osteogenesis of bone mesenchymal stem cells (BMSCs) using a gene point mutant technique. To optimize the function of HIF-1α on inducing stem cells, another constitutively active form of HIF-1α (CA5) was constructed with truncation mutant method and its therapeutic potential on critical-sized bone defects was evaluated with calcium-magnesium phosphate cement (CMPC) scaffold in a rat model. BMSCs were treated with Lenti (lentivirus) -CA5, Lenti-WT (wild-type HIF-1α), and Lenti-LacZ. These genetically modified BMSCs were then combined with CMPC scaffolds to repair critical-sized calvarial defects in rats. The results showed that the overexpression of HIF-1α obviously enhanced the mRNA and protein expression of osteogenic markers in vitro and robust new bone formation with the higher local bone mineral density (BMD) was found in vivo in the CA5 and WT groups. Furthermore, CA5 showed significantly greater stability and osteogenic activity in BMSCs compared with WT. These data suggest that BMSCs transduced with truncation mutanted HIF-1α gene can promote the overexpression of osteogenic markers. CMPC could serve as a potential substrate for HIF-1α gene modified tissue engineered bone to repair critical sized bony defects.
- Subjects :
- Male
Bone Regeneration
Materials science
Angiogenesis
Genetic enhancement
Blotting, Western
Mutant
Biophysics
Bone Marrow Cells
Bioengineering
Mesenchymal Stem Cell Transplantation
Phosphates
Biomaterials
Implants, Experimental
Tissue engineering
Osteogenesis
Transduction, Genetic
Cell Adhesion
Animals
Bone regeneration
Cells, Cultured
Fluorescent Dyes
Bone mineral
Wound Healing
Tissue Scaffolds
Reverse Transcriptase Polymerase Chain Reaction
Skull
Mesenchymal stem cell
Bone Cements
Mesenchymal Stem Cells
X-Ray Microtomography
Alkaline Phosphatase
Hypoxia-Inducible Factor 1, alpha Subunit
Rats, Inbred F344
Rats
Cell biology
Mechanics of Materials
Ceramics and Composites
Stem cell
Biomarkers
Biomedical engineering
Subjects
Details
- ISSN :
- 01429612
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Biomaterials
- Accession number :
- edsair.doi.dedup.....e3de2914557b6b7c6a0c18642708991d