title: Macrophage phagocytosis alters the MRI signal of ferumoxytol-labeled mesenchymal stromal cells in cartilage defects.
abstract: Human mesenchymal stem cells (hMSCs) are a promising tool for cartilage regeneration in arthritic joints. hMSC labeling with iron oxide nanoparticles enables non-invasive in vivo monitoring of transplanted cells in cartilage defects with MR imaging. Since graft failure leads to macrophage phagocytosis of apoptotic cells, we evaluated in vitro and in vivo whether nanoparticle-labeled hMSCs show distinct MR signal characteristics before and after phagocytosis by macrophages. We found that apoptotic nanoparticle-labeled hMSCs were phagocytosed by macrophages while viable nanoparticle-labeled hMSCs were not. Serial MRI scans of hMSC transplants in arthritic joints of recipient rats showed that the iron signal of apoptotic, nanoparticle-labeled hMSCs engulfed by macrophages disappeared faster compared to viable hMSCs. This corresponded to poor cartilage repair outcomes of the apoptotic hMSC transplants. Therefore, rapid decline of iron MRI signal at the transplant site can indicate cell death and predict incomplete defect repair weeks later. Currently, hMSC graft failure can be only diagnosed by lack of cartilage defect repair several months after cell transplantation. The described imaging signs can diagnose hMSC transplant failure more readily, which could enable timely re-interventions and avoid unnecessary follow up studies of lost transplants.
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA, USA.
authors.forename: Hossein
authors.initials: H
authors.lastname: Nejadnik
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Lenkov
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA, USA.
authors.forename: Florian
authors.initials: F
authors.lastname: Gassert
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Fretwell
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Lam
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA, USA.
authors.forename: Heike E
authors.initials: HE
authors.lastname: Daldrup-Link
mesh_terms: D000818:Animals; D002357:Cartilage Diseases / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000628:therapy; D002470:Cell Survival; D003287:Contrast Media; D004195:Disease Models, Animal; D052203:Ferrosoferric Oxide / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000166:cytology*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010587:Phagocytosis; D051381:Rats; D000074084:THP-1 Cells
chemical_list: D003287:Contrast Media; D058185:Magnetite Nanoparticles; D052203:Ferrosoferric Oxide