Recently, the efficacy of therapeutic angiogenesis using VEGF (vascular endothelial growth factor) gene transfer has been reported in human patients with critical limb ischemia and myocardial ischemia.
In case of vascular endothelial growth factor (VEGF), a cytokine secreted from intact cells, bioavailability and meaningful angiogenic bioactivity was shown to be achievable by intramuscular gene transfer in patients with chronic critical limb ischemia.
As part of a phase I clinical trial to document the safety and efficacy of intramuscular gene transfer of naked plasmid DNA-encoding vascular endothelial growth factor (phVEGF165) in the treatment of critical limb ischemia, we treated TAO in 6 patients.
These findings may be cautiously interpreted to indicate that intramuscular injection of naked plasmid DNA achieves constitutive overexpression of VEGF sufficient to induce therapeutic angiogenesis in selected patients with critical limb ischemia.
HIF1α protein levels in the muscles after hind limb ischemia surgery were also significantly lower in BubR1<sup>L/-</sup> mice compared with WT mice (P < .05).
Combined HIF-1α-based gene and cell therapy reduced tissue necrosis even when BMDAC donors and ischemic recipient mice were 17 months old, suggesting that this approach may have therapeutic utility in elderly patients with critical limb ischemia.
Intramuscular injection of an adenovirus encoding a constitutively active form of the HIF-1alpha subunit (CA5) increases the recovery of blood flow following femoral artery ligation in a mouse model of age-dependent critical limb ischemia.
Our results indicate that NOS1177D gene delivery to the ischemic skeletal muscle can be efficient to reverse critical limb ischemia in pathological settings, which are refractory to treatments with a single growth factor, such as vascular endothelial growth factor.
In the present study, we evaluated the therapeutic potential of gene-modified adipose-derived stromal cells (ADSC) that overexpress hepatocyte growth factor (HGF) in a mice hind limb ischemia model.
The current advances of clinical trials of plasmid and adenovirus HGF in the treatment of critical limb ischemia and coronary heart disease in China are introduced.