Dual-modality in vivo monitoring of subventricular zone stem cell migration and metabolism.
Rat subventricular zone (SVZ) stem cells were labeled with superparamagnetic iron oxide particles (SPIO) to follow their fate and migratory potential with magnetic resonance imaging (MRI) and positron emission tomography (PET). Labeled cells were transplanted into either the right rostral migratory stream (RMS) or striatum of normal adult Sprague-Dawley rats and serially followed for 3 months. Minimal migration of the cells implanted into the striatum was observed after 3 weeks whereas SVZ cells implanted into the RMS migrated toward the olfactory bulb at 1 week post-transplantation. PET studies of glucose metabolism using (18)F-FDG demonstrated enhanced glucose utilization in the striatum of transplanted animals. PET studies conducted 3 months after transplantation showed elevated accumulation of (11)C-raclopride (dopamine receptor type 2) and (11)C-CFT (dopamine transporter) binding in the striatal grafts. Implanted SVZ cells did not induce significant inflammation as identified by PET using (11)C-PK11195, a ligand detecting activated microglia. Histological analysis identified viable SPIO-labeled cells (some of which were nestin-positive) 7 weeks post-transplantation, suggesting a prolonged presence of undifferentiated neural stem cells within transplants. In addition, double immunostaining for neuronal and astrocytic markers (NeuN and GFAP) indicated that differentiation into neuronal and astrocytic phenotypes also occurred. Thus, combining MRI and PET enables monitoring of cell migration and metabolism non-invasively in vivo for extended periods of time.
Cicchetti
Francesca
F
Centre de Recherche en Neurosciences, CHUL, RC-9800, 2705 Boulevard Laurier, Québec, Canada G1V 4G2. Francesca.cicchetti@crchul.ulaval.ca
Gross
Robert E
RE
Bulte
Jeff W M
JW
Owen
Mary
M
Chen
Iris
I
Saint-Pierre
Martine
M
Wang
Xukui
X
Yu
Meixiang
M
Brownell
Anna-Liisa
AL
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002247:Carbon Isotopes / Q000494:pharmacology; D002454:Cell Differentiation; D002465:Cell Movement; D017690:Cell Transplantation; D003287:Contrast Media / Q000494:pharmacology*; D005290:Ferric Compounds / Q000494:pharmacology*; D019788:Fluorodeoxyglucose F18 / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009474:Neurons / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000295:instrumentation / Q000379:methods*; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000000981:diagnostic imaging* / Q000473:pathology*
D002247:Carbon Isotopes; D003287:Contrast Media; D005290:Ferric Compounds; D019788:Fluorodeoxyglucose F18; C000499:ferric oxide; D020891:Raclopride; D005947:Glucose