期刊
JOURNAL OF VASCULAR RESEARCH
卷 49, 期 5, 页码 425-431出版社
KARGER
DOI: 10.1159/000337921
关键词
Sonic hedgehog gene therapy; Endothelial progenitor cells; Peripheral ischemia
资金
- Fondazione Roma [RCSNE3]
- Italian Department of University and Research (MIUR) [RBID08-MAFS (FIRB-IDEAS)]
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. Copyright (C) 2012 S. Karger AG, Basel
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