Predicting Angiogenesis by Endothelial Progenitor Cells Relying on In-Vitro Function Assays and VEGFR-2 Expression Levels
Clinical trials have demonstrated the safety and efficacy of autologous endothelial progenitor cell (EPC) therapy in various diseases. Since EPCs’ functions are influenced by genetic, systemic and environmental factors, the therapeutic potential of each individual EPCs is unknown and may a...
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| Format: | Article |
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MDPI AG
2019-11-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/9/11/717 |
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| author | Nadin Sabbah Tal Tamari Rina Elimelech Ofri Doppelt Utai Rudich Hadar Zigdon-Giladi |
| author_facet | Nadin Sabbah Tal Tamari Rina Elimelech Ofri Doppelt Utai Rudich Hadar Zigdon-Giladi |
| author_sort | Nadin Sabbah |
| collection | DOAJ |
| description | Clinical trials have demonstrated the safety and efficacy of autologous endothelial progenitor cell (EPC) therapy in various diseases. Since EPCs’ functions are influenced by genetic, systemic and environmental factors, the therapeutic potential of each individual EPCs is unknown and may affect treatment outcome. Therefore, our aim was to compare EPCs function among healthy donors in order to predict blood vessel formation (angiogenesis) before autologous EPC transplantation. Human EPCs were isolated from the blood of ten volunteers. EPCs proliferation rate, chemoattractant ability, and CXCR4 mRNA levels were different among donors (<i>p</i> < 0.0001, <i>p</i> < 0.01, <i>p</i> < 0.001, respectively). A positive correlation was found between SDF-1, CXCR4, and EPCs proliferation (R = 0.736, <i>p</i> < 0.05 and R = 0.8, <i>p</i> < 0.01, respectively). In-vivo, blood vessels were counted ten days after EPCs transplantation in a subcutaneous mouse model. Mean vessel density was different among donors (<i>p</i> = 0.0001); nevertheless, donors with the lowest vessel densities were higher compared to control (<i>p</i> < 0.05). Finally, using a linear regression model, a mathematical equation was generated to predict blood vessel density relying on: (i) EPCs chemoattractivity, and (ii) VEGFR-2 mRNA levels. Results reveal differences in EPCs functions among healthy individuals, emphasizing the need for a potency assay to pave the way for standardized research and clinical use of human EPCs. |
| first_indexed | 2024-12-12T02:16:42Z |
| format | Article |
| id | doaj.art-4787b823fd974e3aba4e66f8ebf7dac5 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-12T02:16:42Z |
| publishDate | 2019-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-4787b823fd974e3aba4e66f8ebf7dac52022-12-22T00:41:46ZengMDPI AGBiomolecules2218-273X2019-11-0191171710.3390/biom9110717biom9110717Predicting Angiogenesis by Endothelial Progenitor Cells Relying on In-Vitro Function Assays and VEGFR-2 Expression LevelsNadin Sabbah0Tal Tamari1Rina Elimelech2Ofri Doppelt3Utai Rudich4Hadar Zigdon-Giladi5Laboratory for Bone Repair, Rambam Health Care Campus, Haifa 3109600, IsraelLaboratory for Bone Repair, Rambam Health Care Campus, Haifa 3109600, IsraelLaboratory for Bone Repair, Rambam Health Care Campus, Haifa 3109600, IsraelLaboratory for Bone Repair, Rambam Health Care Campus, Haifa 3109600, IsraelThe Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, IsraelLaboratory for Bone Repair, Rambam Health Care Campus, Haifa 3109600, IsraelClinical trials have demonstrated the safety and efficacy of autologous endothelial progenitor cell (EPC) therapy in various diseases. Since EPCs’ functions are influenced by genetic, systemic and environmental factors, the therapeutic potential of each individual EPCs is unknown and may affect treatment outcome. Therefore, our aim was to compare EPCs function among healthy donors in order to predict blood vessel formation (angiogenesis) before autologous EPC transplantation. Human EPCs were isolated from the blood of ten volunteers. EPCs proliferation rate, chemoattractant ability, and CXCR4 mRNA levels were different among donors (<i>p</i> < 0.0001, <i>p</i> < 0.01, <i>p</i> < 0.001, respectively). A positive correlation was found between SDF-1, CXCR4, and EPCs proliferation (R = 0.736, <i>p</i> < 0.05 and R = 0.8, <i>p</i> < 0.01, respectively). In-vivo, blood vessels were counted ten days after EPCs transplantation in a subcutaneous mouse model. Mean vessel density was different among donors (<i>p</i> = 0.0001); nevertheless, donors with the lowest vessel densities were higher compared to control (<i>p</i> < 0.05). Finally, using a linear regression model, a mathematical equation was generated to predict blood vessel density relying on: (i) EPCs chemoattractivity, and (ii) VEGFR-2 mRNA levels. Results reveal differences in EPCs functions among healthy individuals, emphasizing the need for a potency assay to pave the way for standardized research and clinical use of human EPCs.https://www.mdpi.com/2218-273X/9/11/717human endothelial progenitor cellsangiogenesispotency assayconditioned mediumchemoattractantmesenchymal stem cellsvascular endothelial growth factor receptor 2 (vegfr-2) |
| spellingShingle | Nadin Sabbah Tal Tamari Rina Elimelech Ofri Doppelt Utai Rudich Hadar Zigdon-Giladi Predicting Angiogenesis by Endothelial Progenitor Cells Relying on In-Vitro Function Assays and VEGFR-2 Expression Levels Biomolecules human endothelial progenitor cells angiogenesis potency assay conditioned medium chemoattractant mesenchymal stem cells vascular endothelial growth factor receptor 2 (vegfr-2) |
| title | Predicting Angiogenesis by Endothelial Progenitor Cells Relying on In-Vitro Function Assays and VEGFR-2 Expression Levels |
| title_full | Predicting Angiogenesis by Endothelial Progenitor Cells Relying on In-Vitro Function Assays and VEGFR-2 Expression Levels |
| title_fullStr | Predicting Angiogenesis by Endothelial Progenitor Cells Relying on In-Vitro Function Assays and VEGFR-2 Expression Levels |
| title_full_unstemmed | Predicting Angiogenesis by Endothelial Progenitor Cells Relying on In-Vitro Function Assays and VEGFR-2 Expression Levels |
| title_short | Predicting Angiogenesis by Endothelial Progenitor Cells Relying on In-Vitro Function Assays and VEGFR-2 Expression Levels |
| title_sort | predicting angiogenesis by endothelial progenitor cells relying on in vitro function assays and vegfr 2 expression levels |
| topic | human endothelial progenitor cells angiogenesis potency assay conditioned medium chemoattractant mesenchymal stem cells vascular endothelial growth factor receptor 2 (vegfr-2) |
| url | https://www.mdpi.com/2218-273X/9/11/717 |
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