The use of clinically approved small particles of iron oxide (SPIO) for labeling of mesenchymal stem cells aggravates clinical symptoms in experimental autoimmune encephalomyelitis and influences their in vivo distribution.
Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS). Mesenchymal stem cells (MSC) have been shown to ameliorate symptoms in experimental autoimmune encephalomyelitis (EAE), a model of MS. Using cloned MSC labeled with clinically approved small particles of iron oxide (SPIO) for treatment of EAE we analyzed the tissue localization of transferred cells. Treatment with unlabeled MSC led to disease amelioration compared to controls. In contrast, treatment with SPIO-labeled MSC lead to increase in disease severity. Treatment with SPIO alone did not alter disease course. After transplantation labeled and nonlabeled MSC were detected in the CNS and the liver with significantly more SPIO-labeled cells present in the CNS. Iron deposition was present in the group treated with SPIO-labeled MSC, indicating that in vivo the initially cell surface-bound iron detached from the MSC. These results could be of great importance for imaging of patients in the clinical setting, indicating that in vivo application of SPIO-labeled MSC needs to be performed with caution because the cell-derived exposure of iron can lead to disease aggravation.
Schäfer
Richard
R
Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany. richard.schaefer@med.uni-tuebingen.de
Ayturan
Miriam
M
Bantleon
Rüdiger
R
Kehlbach
Rainer
R
Siegel
Georg
G
Pintaske
Joerg
J
Conrad
Sabine
S
Wolburg
Hartwig
H
Northoff
Hinnak
H
Wiskirchen
Jakub
J
Weissert
Robert
R
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000473:pathology / Q000503:physiopathology; D004396:Coloring Agents / Q000009:adverse effects* / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000601:surgery*; D005260:Female; D005290:Ferric Compounds / Q000009:adverse effects* / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D046529:Microscopy, Electron, Transmission; D009103:Multiple Sclerosis / Q000601:surgery; D051381:Rats; D013194:Staining and Labeling / Q000379:methods*
D004396:Coloring Agents; D005290:Ferric Compounds; C000499:ferric oxide