Microgel iron oxide nanoparticles for tracking of stem cells through magnetic resonance imaging

Abstract

<p class=MsoNormal><span lang=EN-US>Current markers for cellular <span class=SpellE>labelling</span> are composite, magnetic particles that measure less than 100 nm or greater than 1 micron in diameter. As the intermediate range has not been investigated, <span class=SpellE>microgel</span> iron oxide particles (MGIO) with the diameters of 89 to 765nm were <span class=SpellE>synthesised</span> and <span class=SpellE>characterised</span> in terms of their physical properties. The magnetic resonance relaxation characteristics of MGIO were measured and shown <span class=GramE>to largely agree</span> with the values predicted by theoretical models.</span>

<p class=MsoNormal><span lang=EN-US>The efficiency of MGIO was tested on human fetal mesenchymal stem cells (<span class=SpellE>fMSC</span>). With simple incubation, MGIO provided equal or better uptake in <span class=SpellE>fMSC</span> compared to a clinical particle, <span class=SpellE>ferucarbotran</span>, with MGIO-600nm achieving three-fold higher uptake. <span class=SpellE>Labelled</span> <span class=SpellE>fMSC</span> was <span class=SpellE>characterised</span> in terms of proliferation rate, <span class=SpellE>multilineage</span> differentiation capacity and global gene expression to show that <span class=SpellE>labelling</span> with MGIO does not affect stem cell functions. <span class=GramE>To further verify</span> the safety of MGIO, human endothelial progenitor cells were <span class=SpellE>labelled</span> and shown to retain phenotype and function after <span class=SpellE>labelling</span>.</span>

<p class=MsoNormal><span lang=EN-US>A rat stroke injury model was developed to observe cellular migration. <span class=SpellE>Labelled-fMSC</span> was transplanted <span class=SpellE>intracerebrally</span> or <span class=SpellE>intraveneously</span> and shown via MRI to home to the injury site. MGIO <span class=SpellE>labelling</span> provided superior detection of cells compared to <span class=SpellE>ferucarbotran</span> <span class=SpellE>labelling</span>. Histological analysis showed that MRI reliably detected the location of <span class=SpellE>fMSC</span> for up to 5 days post-transplantation after which <span class=SpellE>fMSC</span> were rejected by the host due to the nature of the animal model used. This study shows that MGIO is an efficient label that enables improved detection of transplanted cells during in vivo imaging. </span>

<p class=MsoNormal><span lang=EN-US>In all, this thesis describes the development of a high contrast MRI cellular label with superior performance over <span class=SpellE>commericially</span>-available iron particles, with possible applications for <i style='mso-bidi-font-style:normal'>in vivo</i> tracking of transplanted stem cells.</span>