Magnetic Resonance Imaging of Ferumoxytol-Labeled Human Mesenchymal Stem Cells in the Mouse Brain

Abstract

The success of stem cell therapy is highly dependent on accurate delivery of stem cells to the target site of interest. Possible ways to track the distribution of MSCs in vivo include the use of reporter genes or nanoparticles. The U.S. Food and Drug Administration (FDA) has approved ferumoxytol (Feraheme® [USA], Rienso® [UK]) as a treatment for iron deficiency anemia. Ferumoxytol is an ultrasmall superparamagnetic iron oxide nanoparticle (USPIO) that has recently been used to track the fate of transplanted cells using magnetic resonance imaging (MRI). The major objectives of this study were to demonstrate the feasibility of labeling hUCB-MSCs with ferumoxytol and to observe, through MRI, the engraftment of ferumoxytol-labeled human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) delivered via stereotactic injection into the hippocampi of a transgenic mouse model of familial Alzheimer’s disease (5XFAD). Ferumoxytol had no toxic effects on the viability or stemness of hUCB-MSCs when assessed in vitro. Through MRI, hypointense signals were discernible at the site where ferumoxytol-labeled human MSCs were injected. Iron-positive areas were also observed in the engrafted hippocampi. The results from this study support the use of nanoparticle labeling to monitor transplanted MSCs in real time as a follow-up for AD stem cell therapy in the clinical field.Electronic supplementary materialThe online version of this article (doi:10.1007/s12015-016-9694-0) contains supplementary material, which is available to authorized users.

MRI-Tracking of Dental Pulp Stem Cells In Vitro and In Vivo Using Dextran-Coated Superparamagnetic Iron Oxide Nanoparticles

“…Bos et al used MRI for tracking SPIONs-labeled MSCs transfused into the renal arteries and portal veins without any hazardous effect on the viability and differentiation of the injected cells [44]. Lee et al successfully used MRI to track ferumoxytol-labeled MSCs [45]. It was also shown that MSCs labeled with MRI-visible nanoparticles reduced the infarct volume of stroke [46].…”

Mesenchymal stem cells as a multimodal treatment for nervous system diseases

“…Various methods have been developed for intravital imaging 54 . Studies have shown that although the most feasible method of MSC transplantation is through intravenous injection, in such conditions, most of the cells become trapped in the lungs 55 . Nevertheless, such entrapped MSCs can release microvesicles and immunomodulative factors and affect the overall state of the patient by modulating peripheral immune cells 56 .…”

Exploring the Potential of Mesenchymal Stem Cell-Based Therapy in Mouse Models of Vascular Cognitive Impairment

“…The surface markers used to characterize the human MSCs via fluorescence-activated cell sorting (FACS) are illustrated in Figure S2. Immunophenotyping was carried out by referring to previously reported procedures [56,57]. The MSCs used in this present study met the criterion set by the International Society for Cellular Therapy (ISCT) to define MSCs [58].…”