Conditioned medium derived from mesenchymal stem cells overexpressing HPV16 E6E7 dramatically improves ischemic limb
| Autor: | Ming Chau Chang, Shih-Chieh Hung, Paul Chih-Hsueh Chen, Wei Hua Huang, Ching Hua Tsao |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Angiogenesis Papillomavirus E7 Proteins Interleukin-1beta Gene Expression Neovascularization Physiologic Biology Mice Ischemia Fibrosis medicine Animals Humans Neoplastic transformation Molecular Biology Protein kinase B Tube formation Human papillomavirus 16 Mice Inbred BALB C Dissection Mesenchymal stem cell Mesenchymal Stem Cells Oncogene Proteins Viral medicine.disease Cell biology Femoral Artery Repressor Proteins Endothelial stem cell Vascular endothelial growth factor A Thigh Culture Media Conditioned Immunology Cardiology and Cardiovascular Medicine Proto-Oncogene Proteins c-akt |
| Zdroj: | Journal of Molecular and Cellular Cardiology. 72:339-349 |
| ISSN: | 0022-2828 |
| Popis: | Mesenchymal stem cells (MSCs) have been shown to secrete cytokines and growth factors required for angiogenesis. Previously, we demonstrated that MSCs expressing HPV16 E6E7 mRNA (E6E7-MSCs) increase life span and differentiation potential and maintain without neoplastic transformation. Whether E6E7-MSCs are sources of molecules for enhancing angiogenesis is unknown. We demonstrated that E6E7-MSC-derived conditioned medium (E6E7-CM) enhanced endothelial cell migration and tube formation compared to primary MSC-derived conditioned medium (primary-CM). Moreover, E6E7-MSCs increased AKT activation and enhanced the release of Interleukin-1β (IL-1β) and vascular endothelial growth factor A (VEGFA). Neutralization of E6E7-CM with antibodies against IL-1β or VEGFA abrogated its effect in enhancing endothelial migration and tube formation. Primary-CM, added with IL-1β and VEGFA, enhanced its ability to increase endothelial migration and tube formation. E6E7-CM was shown to increase the ability to improve blood perfusion in a mouse limb ischemia model. Histological analysis revealed that E6E7-CM prohibited muscle loss or fibrosis and increased endothelial cell counts compared to primary-CM. Similarly, the effects of E6E7-CM in improving perfusion in ischemic limb were also contributed by the increase of IL-1β or VEGFA levels. These results suggest that E6E7-MSCs increase the ability to secrete angiogenic factors via AKT activation, and E6E7-CM is abundant in IL-1β and VEGFA levels and thereby increases the ability to improve blood perfusion and prohibit muscle loss or fibrosis in a mouse limb ischemia model. |
| Databáze: | OpenAIRE |
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