Magnetic resonance imaging of stem cell–macrophage interactions with ferumoxytol and ferumoxytol‐derived nanoparticles

“Off the shelf” allogeneic stem cell transplants and stem cell nano‐composites are being used for the treatment of degenerative bone diseases. However, major and minor histocompatibility antigens of therapeutic cell transplants can be recognized as foreign and lead to their rejection by the host immune system. If a host immune response is identified within the first week post‐transplant, immune modulating therapies could be applied to prevent graft failure and support engraftment. Ferumoxytol (Feraheme™) is an FDA approved iron oxide nanoparticle preparation for the treatment of anemia in patients. Ferumoxytol can be used “off label” as an magnetic resonance (MR) contrast agent, as these nanoparticles provide measurable signal changes on magnetic resonance imaging (MRI). In this focused review article, we will discuss three methods to localize and identify innate immune responses to stem cell transplants using ferumoxytol‐enhanced MRI, which are based on tracking stem cells, tracking macrophages or detecting mediators of cell death: (a) monitor MRI signal changes of ferumoxytol‐labeled stem cells in the presence or absence of innate immune responses, (b) monitor influx of ferumoxytol‐labeled macrophages into stem cell implants, and (c) monitor apoptosis of stem cell implants with caspase‐3 activatable nanoparticles. These techniques can detect transplant failure at an early stage, when immune‐modulating interventions can potentially preserve the viability of the cell transplants and thereby improve bone and cartilage repair outcomes. Approaches 1 and 2 are immediately translatable to clinical practice. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Cells at the Nanoscale Diagnostic Tools > Biosensing Concept of in vivo and ex vivo stem cell labeling, and value of MR tracking of labeled cells in arthritic joints: (a) ex vivo labelling and (b) in vivo labeling of stem cells before implantation. (c) A failed engraftment of therapeutic cells can be diagnosed 1–2 weeks after the cell transplant based on loss of iron signal at the transplant site (red circle).