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Lauren Cornell, Jennifer McDaniel, Brian Lund, David O. Zamora; Utility of magnetic nanoparticles for targeted endothelial transplantation in an ex vivo model. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1463. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The corneal endothelium is responsible for maintaining corneal clarity. However, this cell layer poses great challenges for clinicians due to its location, lack of regenerative potential, and reducing cell population with age. This study investigates the potential of human corneal endothelial cells (HCEC), loaded with iron-based nanoparticles, to be magnetically-directed to injured regions of the cornea.
Primary cultures of human HCEC were maintained in human endothelial serum free media containing 10 ng/ml FGF-2 and plated at 75,000 cells in a 48 well plate. Cells were then exposed to 50nm dextran-coated biotin conjugated super paramagnetic iron oxide nanoparticles (SPIONP) at 37°C for up to 72 hrs. SPIONP uptake was evaluated via Atomic Emission Spectroscopy (ICP). Mathematical modeling based upon stokes law, gravity, and magnetic field strength was used to determine optimum SPIONP cell loading in relation to magnetic field strength for induced cellular movement within the aqueous chamber. Mathematical modeling efficacy was then evaluated by injecting SPIONP loaded HCECs into a saline chamber in the presence of an applied magnetic field to simulate the anterior chamber of the eye.
HCEC were successfully cultured and maintained their in-vivo cell-specific marker expression of CD200 and Glypican-4, confirming their endothelial lineage. ICP analysis revealed that SPIONP internalization by HCEC was increased by magnetic exposure during cell-MNP loading. When SPIONP loaded-HCEC were injected into the saline chamber at concentrations up to 1 million cells/mL, the cells immediately showed targeted movement through the solution towards the externally applied magnetic field of 1.23 Tesla.
These studies show that HCEC maintained their lineage and readily incorporated SPIONPs without affecting this lineage. Proof of concept studies performed here indicate that cells with internally-loaded SPIONP can be directed and manipulated through an aqueous solution to a predetermined area when a magnetic field is applied. Mathematical modeling of the cell loading capacity and magnetic strength needed for this movement to occur can be an effective tool for tailoring specific therapeutic needs for patients. Results of this study may lead to the development of a non-surgical technique to replenish this vital cell layer.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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