title: Microgel iron oxide nanoparticles for tracking human fetal mesenchymal stem cells through magnetic resonance imaging.
abstract: Stem cell transplantation for regenerative medicine has made significant progress in various injury models, with the development of modalities to track stem cell fate and migration post-transplantation being currently pursued rigorously. Magnetic resonance imaging (MRI) allows serial high-resolution in vivo detection of transplanted stem cells labeled with iron oxide particles, but has been hampered by low labeling efficiencies. Here, we describe the use of microgel iron oxide (MGIO) particles of diameters spanning 100-750 nm for labeling human fetal mesenchymal stem cells (hfMSCs) for MRI tracking. We found that MGIO particle uptake by hfMSCs was size dependent, with 600-nm MGIO (M600) particles demonstrating three- to sixfold higher iron loading than the clinical particle ferucarbotran (33-263 versus 9.6-42.0 pg iron/hfMSC; p < .001). Cell labeling with either M600 particles or ferucarbotran did not affect either cellular proliferation or tri-lineage differentiation into osteoblasts, adipocytes, and chondrocytes, despite differences in gene expression on a genome-wide microarray analysis. Cell tracking in a rat photothrombotic stroke model using a clinical 1.5-T MRI scanner demonstrated the migration of labeled hfMSCs from the contralateral cortex to the stroke injury, with M600 particles achieving a five- to sevenfold higher sensitivity for MRI detection than ferucarbotran (p < .05). However, model-related cellular necrosis and acute inflammation limited the survival of hfMSCs beyond 5-12 days. The use of M600 particles allowed high detection sensitivity with low cellular toxicity to be achieved through a simple incubation protocol, and may thus be useful for cellular tracking using standard clinical MRI scanners.
authors: Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore.
authors: Eddy S M
authors: ES
authors: Lee
authors: Jerry
authors: J
authors: Chan
authors: Borys
authors: B
authors: Shuter
authors: Lay Geok
authors: LG
authors: Tan
authors: Mark S K
authors: MS
authors: Chong
authors: Durrgah L
authors: DL
authors: Ramachandra
authors: Gavin S
authors: GS
authors: Dawe
authors: Jun
authors: J
authors: Ding
authors: Swee Hin
authors: SH
authors: Teoh
authors: Olivier
authors: O
authors: Beuf
authors: Andre
authors: A
authors: Briguet
authors: Kam Chiu
authors: KC
authors: Tam
authors: Mahesh
authors: M
authors: Choolani
authors: Shih-Chang
authors: SC
authors: Wang
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000378:metabolism; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry*; D053686:Fetal Stem Cells / Q000737:chemistry* / Q000166:cytology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000737:chemistry* / Q000166:cytology; D053758:Nanoparticles / Q000737:chemistry*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; C000499:ferric oxide