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Open AccessArticle

Predicting Angiogenesis by Endothelial Progenitor Cells Relying on In-Vitro Function Assays and VEGFR-2 Expression Levels

1
Laboratory for Bone Repair, Rambam Health Care Campus, Haifa 3109600, Israel
2
The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, Israel
3
Department of Periodontology, Rambam Health Care Campus, Haifa 3109601, Israel
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(11), 717; https://doi.org/10.3390/biom9110717
Received: 18 September 2019 / Revised: 4 November 2019 / Accepted: 6 November 2019 / Published: 8 November 2019
(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)
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 (p < 0.0001, p < 0.01, p < 0.001, respectively). A positive correlation was found between SDF-1, CXCR4, and EPCs proliferation (R = 0.736, p < 0.05 and R = 0.8, p < 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 (p = 0.0001); nevertheless, donors with the lowest vessel densities were higher compared to control (p < 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. View Full-Text
Keywords: human endothelial progenitor cells; angiogenesis; potency assay; conditioned medium; chemoattractant; mesenchymal stem cells; vascular endothelial growth factor receptor 2 (VEGFR-2) human endothelial progenitor cells; angiogenesis; potency assay; conditioned medium; chemoattractant; mesenchymal stem cells; vascular endothelial growth factor receptor 2 (VEGFR-2)
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Sabbah, N.; Tamari, T.; Elimelech, R.; Doppelt, O.; Rudich, U.; Zigdon-Giladi, H. Predicting Angiogenesis by Endothelial Progenitor Cells Relying on In-Vitro Function Assays and VEGFR-2 Expression Levels. Biomolecules 2019, 9, 717.

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