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Combination of HIF-1α gene transfection and HIF-1-activated bone marrow-derived angiogenic cell infusion improves burn wound healing in aged mice.
- Source :
-
Gene therapy [Gene Ther] 2013 Nov; Vol. 20 (11), pp. 1070-6. Date of Electronic Publication: 2013 Jun 20. - Publication Year :
- 2013
-
Abstract
- Impaired burn wound healing in the elderly represents a major clinical problem. Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator that orchestrates the cellular response to hypoxia. Its actions in dermal wounds promote angiogenesis and improve healing. In a murine burn wound model, aged mice had impaired wound healing associated with reduced levels of HIF-1. When gene therapy with HIF-1 alone did not correct these deficits, we explored the potential benefit of HIF-1 gene therapy combined with the intravenous infusion of bone marrow-derived angiogenic cells (BMDACs) cultured with dimethyloxalylglycine (DMOG). DMOG is known to reduce oxidative degradation of HIF-1. The mice treated with a plasmid DNA construct expressing a stabilized mutant form of HIF-1α (CA5-HIF-1α)+BMDACs had more rapid wound closure. By day 17, there were more mice with completely closed wounds in the treated group (χ(2), P=0.05). The dermal blood flow measured by laser Doppler showed significantly increased wound perfusion on day 11. Homing of BMDACs to the burn wound was dramatically enhanced by CA5-HIF-1α gene therapy. HIF-1α mRNA expression in the burn wound was increased after transfection with CA5-HIF-1α plasmid. Our findings offer insight into the pathophysiology of burns in the elderly and point to potential targets for developing new therapeutic strategies.
- Subjects :
- Adenoviridae genetics
Aging
Animals
Burns genetics
Burns therapy
Cells, Cultured
Combined Modality Therapy
Disease Models, Animal
Female
Genetic Vectors
Humans
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Male
Mice
Mice, Inbred C57BL
Neovascularization, Physiologic
Wound Healing
Bone Marrow Cells metabolism
Bone Marrow Transplantation
Burns physiopathology
Genetic Therapy
Hypoxia-Inducible Factor 1, alpha Subunit genetics
Transfection
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5462
- Volume :
- 20
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 23784441
- Full Text :
- https://doi.org/10.1038/gt.2013.32