Magnetic resonance tracking of transplanted bone marrow and embryonic stem cells labeled by iron oxide nanoparticles in rat brain and spinal cord.
Nuclear magnetic resonance (MR) imaging provides a noninvasive method for studying the fate of transplanted cells in vivo. We studied, in animals with a cortical photochemical lesion or with a balloon-induced spinal cord compression lesion, the fate of implanted rat bone marrow stromal cells (MSCs) and mouse embryonic stem cells (ESCs) labeled with superparamagnetic iron oxide nanoparticles (Endorem). MSCs were colabeled with bromodeoxyuridine (BrdU), and ESCs were transfected with pEGFP-C1 (eGFP ESCs). Cells were either grafted intracerebrally into the contralateral hemisphere of the adult rat brain or injected intravenously. In vivo MR imaging was used to track their fate; Prussian blue staining and electron microscopy confirmed the presence of iron oxide nanoparticles inside the cells. During the first week postimplantation, grafted cells migrated to the lesion site and populated the border zone of the lesion. Less than 3% of MSCs differentiated into neurons and none into astrocytes; 5% of eGFP ESCs differentiated into neurons, whereas 70% of eGFP ESCs became astrocytes. The implanted cells were visible on MR images as a hypointense area at the injection site, in the corpus callosum and in the lesion. The hypointense signal persisted for more than 50 days. The presence of GFP-positive or BrdU-positive and nanoparticle-labeled cells was confirmed by histological staining. Our study demonstrates that both grafted MSCs and eGFP ESCs labeled with a contrast agent based on iron oxide nanoparticles migrate into the injured CNS. Iron oxide nanoparticles can therefore be used as a marker for the long-term noninvasive MR tracking of implanted stem cells.
Jendelová
Pavla
P
Institute of Experimental Medicine Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Herynek
Vít
V
Urdzíková
Lucia
L
Glogarová
Katerina
K
Kroupová
Jana
J
Andersson
Benita
B
Bryja
Vítezslav
V
Burian
Martin
M
Hájek
Milan
M
Syková
Eva
E
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000648:ultrastructure; D016026:Bone Marrow Transplantation / Q000379:methods; D001921:Brain / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005290:Ferric Compounds / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry / Q000379:methods; D008164:Luminescent Proteins / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008854:Microscopy, Electron / Q000379:methods; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation / Q000648:ultrastructure; D013117:Spinal Cord Compression / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000378:metabolism* / Q000648:ultrastructure
D005290:Ferric Compounds; D005904:Glial Fibrillary Acidic Protein; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; C000499:ferric oxide; D010751:Phosphopyruvate Hydratase