Focused Magnetic Stem Cell Targeting to the Retina Using Superparamagnetic Iron Oxide Nanoparticles

Abstract

Developing new ways of delivering cells to diseased tissue will be a key factor in translating cell therapeutics research into clinical use. Magnetically targeting cells enables delivery of significant numbers of cells to key areas of specific organs. To demonstrate feasibility in neurological tissue, we targeted cells magnetically to the upper hemisphere of the rodent retina. Rat mesenchymal stem cells (MSCs) were magnetized using superparamagnetic iron oxide nanoparticles (SPIONs). In vitro studies suggested that magnetization with fluidMAG-D was well tolerated, that cells remained viable, and they retained their differentiation capabilities. FluidMAG-D-labeled MSCs were injected intravitreally or via the tail vein of the S334ter-4 transgenic rat model of retinal degeneration with or without placing a gold-plated neodymium disc magnet within the orbit, but outside the eye. Retinal flatmount and cryosection imaging demonstrated that after intravitreal injection cells localized to the inner retina in a tightly confined area corresponding to the position of the orbital magnet. After intravenous injection, similar retinal localization was achieved and remarkably was associated with a tenfold increase in magnetic MSC delivery to the retina. Cryosections demonstrated that cells had migrated into both the inner and outer retina. Magnetic MSC treatment with orbital magnet also resulted in significantly higher retinal concentrations of anti-inflammatory molecules interleukin-10 and hepatocyte growth factor. This suggested that intravenous MSC therapy also resulted in significant therapeutic benefit in the dystrophic retina. With minimal risk of collateral damage, these results suggest that magnetic cell delivery is the best approach for controlled delivery of cells to the outer retina-the focus for disease in age-related macular degeneration and retinitis pigmentosa.

Mesenchymal stem cell therapy of hepatocellular carcinoma in rats: Detection of cell homing and tumor mass by magnetic resonance imaging using iron oxide nanoparticles

“…11 To improve the ability of these particles to be endocytosed by MSCs, poly-l-lysine was utilized as a prospective vehicle for iron oxide nanoparticle transport into cells. 12 MSCs were counted, then seeded in micro-well plates at the density of 10 5 cells/well in a culture medium.…”

Improved Imaging of Magnetically Labeled Cells Using Rotational Magnetomotive Optical Coherence Tomography

“…For this, we magnetically labeled mesenchymal stem cells (MSCs) with the fluorescent magnetic particles, as mentioned in Section 3.1, and embedded them in agar scaffolds resembling the elastic properties of soft tissue, as described in [6]. Concerning cellular particle load and its effect on cell function, recent literature indicates that MSCs incubated with 200-nm magnetic particles coated with dextran-sulfate take up ~10 pg of iron oxide per cell, and show a cell viability of ~70% after 24 h [12]. After preparation, we placed the samples on the object stage of our multimodal imaging setup containing the permanent magnet and kept them under resting conditions for 30 min in order to provoke the formation and alignment of magnetic chains inside the cells.…”

Development Status in the Meadow of Nanostructure Magnetic Drug Delivery System and Its Promising Applications

“…Characterized by pluripotency, (capacity to differentiate into a plethora of specialized cells) and confer therapeutic benefits that have catalyzed the meadow of regenerative medicine [35][36]. Their application for treatment of retinal degenerations, spinal cord injuries and brain traumas [37][38][39]. Magnetically responsive nanoparticles are biocompatible and employ for targeted delivery of stem cells for improvement in their retention in targeted site.…”