Magnetically Guided Intravenous Mesenchymal Stem Cells Result In Enhanced Retinal Preservation In Dystrophic Rodents

Abstract

Purpose: : To determine the value of systemically delivered MSCs in inhibiting retinal degeneration in a rodent model. In our previous studies we have shown that magnetizing mesenchymal stem cells (MSCs) significantly improves their delivery to the retina via the systemic circulation. We have also shown that these cells accumulate within the outer as well as inner retina. Their innate neuroprotective and anti-inflammatory capacity highlight MSC’s as a potential therapy for retinal dystrophy.

Methods: : MSCs were harvested from syngeneic rat inguinal adipose tissue and incubated with dextran-coated 100nm magnetic nanoparticles (fluidMAG-D). A 3mm gold-plated neodymium disc magnet was positioned within the orbit, but outside the globe in selected heterozygous S334ter-4 rhodopsin-mutant rats. One million magnetized MSCs were injected into the rat tail vein at post-natal day 21. Cohorts were treated with either a sham injection (no orbital magnet), a single injection of magnetized MSCs but no orbital magnet, a single injection of magnetized MSC with an orbital magnet in place or multiple monthly injections of magnetized MSCs also with an orbital magnet in place. Results were compared up to post-natal day 110. Effects were assessed using serial in vivo optical coherence tomography, electroretinography and optokinetic tracking responses. Immunohistochemistry studies were undertaken at the end of the study period.

Results: : Multiple monthly magnetized MSC injections provided the most significantly enhanced retinal preservation. Dark-adapted maximal electroretinogram b wave amplitudes and spatial frequency thresholds showed a greater than twofold improvement in preserving vision in comparison with results obtained with a single non-magnetic MSC injection. These functional benefits correlated with anatomical preservation in the outer nuclear layer.

Conclusions: : The systemic administration of magnetized MSCs not only allows for accumulation of large numbers of cells at specific retinal loci, but also improved photoreceptor survival, warranting further investigation into this novel delivery technique.

Keywords: neuroprotection • retinal degenerations: hereditary • electroretinography: non-clinical