Abstract
This study evaluated the potential of iron oxide nanoparticle-loaded human embryonic stem cell (ESC)-derived spherical neural masses (SNMs) to improve the transportation of stem cells to the brain, ameliorate brain damage from intracerebral hemorrhage (ICH), and recover the functional status after ICH under an external magnetic field of a magnet attached to a helmet. At 24 h after induction of ICH, rats were randomly separated into three experimental groups: ICH with injection of phosphate-buffered saline (PBS group), ICH with intravenous injection of magnetosome-like ferrimagnetic iron oxide nanocubes (FION)-labeled SNMs (SNMs* group), and ICH with intravenous injection of FION-labeled SNMs followed by three days of external magnetic field exposure for targeted delivery by a magnet-embedded helmet (SNMs*+Helmet group). On day 3 after ICH induction, an increased Prussian blue-stained area and decreased swelling volume were observed in the SNMs*+Helmet group compared with that of the other groups. A significantly decreased recruitment of macrophages and neutrophils and a downregulation of pro-inflammatory cytokines followed by improved neurological function three days after ICH were observed in the SNMs*+Helmet group. Hemispheric atrophy at six weeks after ICH was significantly decreased in the SNMs*+Helmet group compared with that of the PBS group. In conclusion, we have developed a targeted delivery system using FION tagged to stem cells and a magnet-embedded helmet. The targeted delivery of SNMs might have the potential for developing novel therapeutic strategies for ICH.
Highlights
Spontaneous intracerebral hemorrhage (ICH) accounts for 10–20% of all strokes, but are disproportionately responsible for 40% of case fatality and 60% of functional dependency after stroke [1]
We determined the toxic effect of the ferrimagnetic iron oxide nanocubes (FION) on the spherical neural masses (SNMs) using the cell counting kit-8 (CCK-8) assay
There was no significant difference between the numbers of cells in the control vs. the presence of the 20 μg/mL and 40 μg/mL FIONs on days 1, 3, and 5
Summary
Spontaneous intracerebral hemorrhage (ICH) accounts for 10–20% of all strokes, but are disproportionately responsible for 40% of case fatality and 60% of functional dependency after stroke [1]. There are no effective radical therapies for restoring independence and quality of life after ICH. There are only conservative treatments including the control of blood pressure, osmotic therapy for perihematomal edema, and life-saving surgical management and rehabilitation [2]. It has been postulated that stem cell administration could alleviate the primary and secondary effects of ICH via anti-inflammation, anti-apoptosis, promotion of neurogenesis and angiogenesis, and tissue repair or replacement [3,4,5]. Specific guidelines on the types, cell counts, effective time window, and route for administration of stem cell therapy in ICH treatment are not well established. Careful consideration of strategies for effective stem cell therapy is needed
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