Superparamagnetic iron oxide-labeled Schwann cells and olfactory ensheathing cells can be traced in vivo by magnetic resonance imaging and retain functional properties after transplantation into the CNS.
Schwann cell (SC) and olfactory ensheathing cell (OEC) transplantation has been shown experimentally to promote CNS axonal regeneration and remyelination. To advance this technique into a clinical setting it is important to be able to follow the fates of transplanted cells by noninvasive imaging. Previous studies, using complex modification processes to enable uptake of contrast agents, have shown that cells labeled in vitro with paramagnetic contrast agents transplanted into rodent CNS can be visualized using magnetic resonance imaging (MRI). Here we show that SCs and OECs efficiently internalize dextran-coated superparamagnetic iron oxide (SPIO) from the culture medium by fluid phase pinocytosis. After transplantation into focal areas of demyelination in adult rat spinal cord both transplanted SPIO-labeled SCs and OECs produce a signal reduction using T(2)-weighted MRI in anesthetized rats that persists for up to 4 weeks. Although signal reduction was discernable after transplantation of unlabelled cells, this is nevertheless distinguishable from that produced by transplanted labeled cells. The region of signal reduction in SPIO-labeled cell recipients correlates closely with areas of remyelination. Because the retention of functional integrity by labeled cells is paramount, we also show that SPIO-labeled SCs and OECs are able to myelinate normally after transplantation into focal areas of demyelination. These studies demonstrate the feasibility of noninvasive imaging of transplanted SCs and OECs and represent a significant step toward the clinical application of promising experimental approaches.
Dunning
Mark D
MD
Cambridge Center for Brain Repair and Neuroregeneration Laboratory, Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom.
Lakatos
Andras
A
Loizou
Louiza
L
Kettunen
Mikko
M
ffrench-Constant
Charles
C
Brindle
Kevin M
KM
Franklin
Robin J M
RJ
D000818:Animals; D016380:Brain Tissue Transplantation / Q000502:physiology; D017690:Cell Transplantation / Q000502:physiology*; D003711:Demyelinating Diseases / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D052203:Ferrosoferric Oxide; D007501:Iron; D008279:Magnetic Resonance Imaging; D008297:Male; D009186:Myelin Sheath / Q000502:physiology; D049329:Nanostructures; D009416:Nerve Regeneration / Q000502:physiology; D009830:Olfactory Bulb / Q000166:cytology*; D010087:Oxides; D010873:Pinocytosis; D051381:Rats; D011916:Rats, Inbred F344; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*
D010087:Oxides; D007501:Iron; D052203:Ferrosoferric Oxide