In vivo tracking of stem cells in brain and spinal cord injury. 2007

Eva Sykova, and Pavla Jendelova
Institute of Experimental Medicine ASCR, EU Centre of Excellence, Prague, Czech Republic. sykova@biomed.cas.cz

Cellular magnetic resonance (MR) imaging is a rapidly growing field that aims to visualize and track cells in living organisms. Superparamagnetic iron oxide (SPIO) nanoparticles offer a sufficient signal for T2 weighted MR images. We followed the fate of embryonic stem cells (ESCs) and bone marrow mesenchymal stem cells (MSCs) labeled with iron oxide nanoparticles (Endorem) and human CD34+ cells labeled with magnetic MicroBeads (Miltenyi) in rats with a cortical or spinal cord lesion, models of stroke and spinal cord injury (SCI), respectively. Cells were either grafted intracerebrally, contralaterally to a cortical photochemical lesion, or injected intravenously. During the first post-transplantation week, grafted MSCs or ESCs migrated to the lesion site in the cortex as well as in the spinal cord and were visible in the lesion on MR images as a hypointensive signal, persisting for more than 30 days. In rats with an SCI, we found an increase in functional recovery after the implantation of MSCs or a freshly prepared mononuclear fraction of bone marrow cells (BMCs) or after an injection of granulocyte colony stimulating factor (G-CSF). Morphometric measurements in the center of the lesions showed an increase in white matter volume in cell-treated animals. Prussian blue staining confirmed a large number of iron-positive cells, and the lesions were considerably smaller than in control animals. Additionally, we implanted hydrogels based on poly-hydroxypropylmethacrylamide (HPMA) seeded with nanoparticle-labeled MSCs into hemisected rat spinal cords. Hydrogels seeded with MSCs were visible on MR images as hypointense areas, and subsequent Prussian blue histological staining confirmed positively stained cells within the hydrogels. To obtain better results with cell labeling, new polycation-bound iron oxide superparamagnetic nanoparticles (PC-SPIO) were developed. In comparison with Endorem, PC-SPIO demonstrated a more efficient intracellular uptake into MSCs, with no decrease in cell viability. Our studies demonstrate that magnetic resonance imaging (MRI) of grafted adult as well as ESCs labeled with iron oxide nanoparticles is a useful method for evaluating cellular migration toward a lesion site.

UI MeSH Term Description Entries
D001930 Brain Injuries Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits. Brain Lacerations,Acute Brain Injuries,Brain Injuries, Acute,Brain Injuries, Focal,Focal Brain Injuries,Injuries, Acute Brain,Injuries, Brain,Acute Brain Injury,Brain Injury,Brain Injury, Acute,Brain Injury, Focal,Brain Laceration,Focal Brain Injury,Injuries, Focal Brain,Injury, Acute Brain,Injury, Brain,Injury, Focal Brain,Laceration, Brain,Lacerations, Brain
D003584 Cytological Techniques Methods used to study CELLS. Cytologic Technics,Cytological Technic,Cytological Technics,Cytological Technique,Technic, Cytological,Technics, Cytological,Technique, Cytological,Techniques, Cytological,Cytologic Technic,Technic, Cytologic,Technics, Cytologic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013119 Spinal Cord Injuries Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., WOUNDS, GUNSHOT; WHIPLASH INJURIES; etc.). Myelopathy, Traumatic,Injuries, Spinal Cord,Post-Traumatic Myelopathy,Spinal Cord Contusion,Spinal Cord Laceration,Spinal Cord Transection,Spinal Cord Trauma,Contusion, Spinal Cord,Contusions, Spinal Cord,Cord Contusion, Spinal,Cord Contusions, Spinal,Cord Injuries, Spinal,Cord Injury, Spinal,Cord Laceration, Spinal,Cord Lacerations, Spinal,Cord Transection, Spinal,Cord Transections, Spinal,Cord Trauma, Spinal,Cord Traumas, Spinal,Injury, Spinal Cord,Laceration, Spinal Cord,Lacerations, Spinal Cord,Myelopathies, Post-Traumatic,Myelopathies, Traumatic,Myelopathy, Post-Traumatic,Post Traumatic Myelopathy,Post-Traumatic Myelopathies,Spinal Cord Contusions,Spinal Cord Injury,Spinal Cord Lacerations,Spinal Cord Transections,Spinal Cord Traumas,Transection, Spinal Cord,Transections, Spinal Cord,Trauma, Spinal Cord,Traumas, Spinal Cord,Traumatic Myelopathies,Traumatic Myelopathy
D053758 Nanoparticles Nanometer-sized particles that are nanoscale in three dimensions. They include nanocrystaline materials; NANOCAPSULES; METAL NANOPARTICLES; DENDRIMERS, and QUANTUM DOTS. The uses of nanoparticles include DRUG DELIVERY SYSTEMS and cancer targeting and imaging. Nanocrystalline Materials,Nanocrystals,Material, Nanocrystalline,Materials, Nanocrystalline,Nanocrystal,Nanocrystalline Material,Nanoparticle
D020100 Hydrogels Water swollen, rigid, 3-dimensional network of cross-linked, hydrophilic macromolecules, 20-95% water. They are used in paints, printing inks, foodstuffs, pharmaceuticals, and cosmetics. (Grant & Hackh's Chemical Dictionary, 5th ed) Hydrogel,In Situ Hydrogel,In Situ Hydrogels,Patterned Hydrogel,Patterned Hydrogels,Hydrogel, In Situ,Hydrogel, Patterned
D020521 Stroke A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810) Apoplexy,Cerebral Stroke,Cerebrovascular Accident,Cerebrovascular Apoplexy,Vascular Accident, Brain,CVA (Cerebrovascular Accident),Cerebrovascular Accident, Acute,Cerebrovascular Stroke,Stroke, Acute,Acute Cerebrovascular Accident,Acute Cerebrovascular Accidents,Acute Stroke,Acute Strokes,Apoplexy, Cerebrovascular,Brain Vascular Accident,Brain Vascular Accidents,CVAs (Cerebrovascular Accident),Cerebral Strokes,Cerebrovascular Accidents,Cerebrovascular Accidents, Acute,Cerebrovascular Strokes,Stroke, Cerebral,Stroke, Cerebrovascular,Strokes,Strokes, Acute,Strokes, Cerebral,Strokes, Cerebrovascular,Vascular Accidents, Brain
D033581 Stem Cell Transplantation The transfer of STEM CELLS from one individual to another within the same species (TRANSPLANTATION, HOMOLOGOUS) or between species (XENOTRANSPLANTATION), or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). The source and location of the stem cells determines their potency or pluripotency to differentiate into various cell types. Transplantation, Stem Cell,Stem Cell Transplantations,Transplantations, Stem Cell

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