Magnetic Field Dynamic Strategies for the Improved Control of the Angiogenic Effect of Mesenchymal Stromal Cells.

Ana C Manjua,Frederico Castelo Ferreira,Joaquim M S Cabral,Carla A M Portugal

doi:10.3390/polym13111883

Abstract

This work shows the ability to remotely control the paracrine performance of mesenchymal stromal cells (MSCs) in producing an angiogenesis key molecule, vascular endothelial growth factor (VEGF-A), by modulation of an external magnetic field. This work compares for the first time the application of static and dynamic magnetic fields in angiogenesis in vitro model, exploring the effect of magnetic field intensity and dynamic regimes on the VEGF-A secretion potential of MSCs. Tissue scaffolds of gelatin doped with iron oxide nanoparticles (MNPs) were used as a platform for MSC proliferation. Dynamic magnetic field regimes were imposed by cyclic variation of the magnetic field intensity in different frequencies. The effect of the magnetic field intensity on cell behavior showed that higher intensity of 0.45 T was associated with increased cell death and a poor angiogenic effect. It was observed that static and dynamic magnetic stimulation with higher frequencies led to improved angiogenic performance on endothelial cells in comparison with a lower frequency regime. This work showed the possibility to control VEGF-A secretion by MSCs through modulation of the magnetic field, offering attractive perspectives of a non-invasive therapeutic option for several diseases by revascularizing damaged tissues or inhibiting metastasis formation during cancer progression.

Highlights

The formation of new blood vessels from existing ones is relatively rare in adults and occurs mostly in post-injury regeneration areas or during tumor growth [1]
Cell proliferation studies showed that the increase of the magnetic field intensity from 0.08 T to 0.45 T led to a decrease of the number of cells, observed either for mesenchymal stromal cells (MSCs) cultured in mGelatin scaffolds as well as for MSCs monolayers cultured in polystyrene cell plates
Lower magnetic field intensity (0.08 T), as well as a high-frequency magnetic variation regime, resulted in the increased production of growth factor VEGF-A compared to that observed at a magnetic field with a higher intensity (0.45 T) or applied under low frequency modes (LF modes), which translated into a positive angiogenic effect in Human Umbilical Vein Endothelial Cells (HUVECs) with the formation of a high number of tubes and branch points

Summary

Introduction

The formation of new blood vessels from existing ones (angiogenesis) is relatively rare in adults and occurs mostly in post-injury regeneration areas or during tumor growth [1]. These two types of angiogenesis are promoted by similar angiogenic signals, the application outcomes are very different. Among the key features of the angiogenic mechanism are temporal regulation, the spatial organization of the stimuli, cellular crosstalk, active remodeling, and interaction with the extracellular matrix [5,6] When these features are dysregulated, the development of new vasculature is abnormal (e.g., tumor angiogenesis). Anti-angiogenic procedures are being exhaustively investigated mainly to reduce tumor growth in cancer patients [5,6]

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