Mapping transplanted stem cell migration after a stroke: a serial, in vivo magnetic resonance imaging study.
Preferential migration of stem cells toward the site of a lesion is a highly desirable property of stem cells that allows flexibility in the site of graft implantation in the damaged brain. In rats with unilateral stroke damage, neural stem cells transplanted into the contralateral hemisphere migrate across to the lesioned hemisphere and populate the area around the ischaemic infarct. To date, the migration of neural stem cells in the damaged brain has been mainly inferred from snapshot histological images. In this study, we demonstrate that by pre-labelling neural stem cells with the bimodal contrast agent Gadolinium-RhodamIne Dextran [GRID, detectable by both magnetic resonance imaging (MRI) and fluorescent microscopy], the transhemispheric migration of transplanted neural stem cells contralateral to a stroke lesion can be followed in vivo by serial MRI and corroborated by subsequent histological analyses. Our results indicate that neural stem cells migrated from the injection tract mainly along the corpus callosum within 7 days of transplantation and extensively re-populated the peri-lesion area by 14 days following implantation. In contrast, neural stem cells transplanted into sham controls did not show any substantial migration outside of the injection tract, suggesting that the transcallosal migration observed in the stroke-lesioned animals is due to neural stem cells being attracted by the lesion site. In vivo tracking of the migration of neural stem cells responding to damage will greatly enhance our understanding of optimal transplantation strategies as well as how neural stem cells promote functional and anatomical recovery in neurological disorders.
Modo
Michel
M
Neuroimaging Research Group-Neurology P042, Institute of Psychiatry, King's College London, SE5 8AF, London, UK. m.modo@iop.kcl.ac.uk
Mellodew
Karen
K
Cash
Diana
D
Fraser
Scott E
SE
Meade
Thomas J
TJ
Price
Jack
J
Williams
Steven C R
SC
D000818:Animals; D001925:Brain Damage, Chronic / Q000473:pathology / Q000503:physiopathology*; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D003287:Contrast Media / Q000008:administration & dosage; D003337:Corpus Callosum / Q000473:pathology; D003911:Dextrans; D004292:Dominance, Cerebral / Q000502:physiology*; D019786:Gadolinium DTPA; D006624:Hippocampus / Q000166:cytology; D007089:Image Enhancement / Q000379:methods*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012235:Rhodamines; D033581:Stem Cell Transplantation
D003287:Contrast Media; D003911:Dextrans; D012235:Rhodamines; D019786:Gadolinium DTPA