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Combined Therapy with Sonic Hedgehog Gene Transfer and Bone Marrow-Derived Endothelial Progenitor Cells Enhances Angiogenesis and Myogenesis in the Ischemic Skeletal Muscle
- Publication Year :
- 2012
-
Abstract
- We have previously demonstrated that sonic hedgehog (Shh) gene transfer improves angiogenesis in the setting of ischemia by upregulating the expression of multiple growth factors and enhancing the incorporation of endogenous bone marrow (BM)-derived endothelial progenitor cells (EPCs). In this study, we hypothesized that combined therapy with Shh gene transfer and BM-derived EPCs is more effective than Shh gene therapy alone in an experimental model of peripheral limb ischemia. We used old mice, which have a significantly reduced angiogenic response to ischemia, and compared the ability of Shh gene transfer, exogenous EPCs, or both to improve regeneration after ischemia. We found a significantly higher capillary density in the Shh + EPC-treated muscles compared to the other experimental groups. We also found that Shh gene transfer increases the incorporation and survival of transplanted EPCs. Finally, we found a significantly higher number of regenerating myofibers in the ischemic muscles of mice receiving combined treatment with Shh and BM-derived EPCs. In summary, the combination of Shh gene transfer and BM-derived EPCs more effectively promotes angiogenesis and muscle regeneration than each treatment individually and merits further investigation for its potential beneficial effects in ischemic diseases.
- Subjects :
- Male
animal structures
Physiology
Angiogenesis
Genetic enhancement
Ischemia
Neovascularization, Physiologic
Bone Marrow Cells
Biology
Muscle Development
Shh
Mice
angiogenesis
medicine
Animals
Regeneration
Hedgehog Proteins
myogenesi
Sonic hedgehog
Progenitor cell
Muscle, Skeletal
Bone Marrow Transplantation
endothelial progenitor cells
Myogenesis
Regeneration (biology)
Settore MED/09 - MEDICINA INTERNA
angiogenesi
Endothelial Cells
Genetic Therapy
medicine.disease
Hindlimb
Mice, Inbred C57BL
medicine.anatomical_structure
embryonic structures
cardiovascular system
biology.protein
Cancer research
Bone marrow
myogenesis
Cardiology and Cardiovascular Medicine
circulatory and respiratory physiology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....358d650e544eb9b043b7c795be1321d9