Genetically modified bone marrow mesenchymal stem cells and dental pulp mesenchymal stem cells by HIF-1alpha overexpression, differs in survival and angiogenic effects after in animal model of hind limb ischemia

Abstract

In many clinical trials, mesenchymal stem cells (MSCs) are used to treat vital organ ischemia, primarily because of their ability to secrete signals that trigger vascularization. However, their effect is limited, probably because these paracrine signals are secreted at a sub-therapeutic rate.In these studies, a combination of cell and gene therapy using BMSCs and DPMSCs transfected with a eukaryotic expression vector HA HIF1alpha-pcDNA3 plasmid, a pro-angiogenic factor, increased VEGF, and CCL5. HIF1alpha-hBMSC and HIF1alpha-hDPMC accelerated the improvement of tissue function and ischemia on days 7 and 14 compared with control groups. In terms of evaluation, the persistence and proliferation of the vector inside the cell was identified up to day 7. Also in terms of cell viability, HIF1alpha-hDPMC cell was identified up to day 21, and HIF1alpha-hBMSC was detected up to day 28. Comparison of these two cells showed that HIF1alpha-hBMSC had a greater effect on increasing VEGF expression as well as accelerating the improvement of cell function and survival than HIF1alpha-hDPMC. Our results show that the use of genetic modification stem cells or HIF1 genes due to increased VEGF gene expression can be effective in the treatment of Critical hind limb ischemia.