In vivo magnetic resonance imaging tracks adult neural progenitor cell targeting of brain tumor

Using magnetic resonance imaging (MRI), we described a method for noninvasively tracking grafted neural progenitor cells and bone marrow stromal cells (MSCs) in brain tumor of the rat. Neural progenitor cells and MSCs were labeled with lipophilic dye-coated superparamagnetic particles. The labeled neural progenitor cells and MSCs were transplanted to rats via the cisterna magna and a tail vein, respectively, 1 week after 9L-gliosarcoma cell implantation. Three-dimensional (3D) gradient echo and contrast agent images revealed dynamic migration of adult neural progenitor cells and MSCs detected by loss of MRI signals towards tumor mass and infiltrated tumor cells. Prussian blue staining and fluorescent microscope analysis showed that grafted cells targeted tumor cells and areas with grafted cells corresponded to areas with loss of MRI signals. These results demonstrate that the MRI technique provides a sensitive method for in vivo assessment of grafted cells targeting tumor mass and infiltrated tumor cells and that adult neural progenitor cells and MSCs can target tumor aggregates in the brain.

[1]  G. Finocchiaro,et al.  Gene therapy of experimental brain tumors using neural progenitor cells , 2000, Nature Medicine.

[2]  P. Black,et al.  Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[3]  M. Tessier-Lavigne,et al.  The chemokine SDF1 regulates migration of dentate granule cells. , 2002, Development.

[4]  Jeff W M Bulte,et al.  In Vivo Magnetic Resonance Tracking of Magnetically Labeled Cells after Transplantation , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[5]  L. Lilge,et al.  Photodynamic Therapy of 9L Gliosarcoma with Liposome‐Delivered Photofrin , 1997, Photochemistry and photobiology.

[6]  K. Black,et al.  The use of interleukin 12-secreting neural stem cells for the treatment of intracranial glioma. , 2002, Cancer research.

[7]  M. Chopp,et al.  Therapeutic Benefit of Intravenous Administration of Bone Marrow Stromal Cells After Cerebral Ischemia in Rats , 2001, Stroke.

[8]  M. Noble Can neural stem cells be used to track down and destroy migratory brain tumor cells while also providing a means of repairing tumor-associated damage? , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Peter McL Black,et al.  The Neurosurgeon as Local Oncologist: Cellular and Molecular Neurosurgery in Malignant Glioma Therapy , 2003, Neurosurgery.

[10]  M Chopp,et al.  Migration and differentiation of adult rat subventricular zone progenitor cells transplanted into the adult rat striatum , 2003, Neuroscience.

[11]  H. Fine,et al.  Cellular and genetic characterization of human adult bone marrow-derived neural stem-like cells: a potential antiglioma cellular vector. , 2003, Cancer research.

[12]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[13]  Ying Wang,et al.  Activated Neural Stem Cells Contribute to Stroke-Induced Neurogenesis and Neuroblast Migration toward the Infarct Boundary in Adult Rats , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[14]  S. Dudas,et al.  Identification and localization of the cytokine SDF1 and its receptor, CXC chemokine receptor 4, to regions of necrosis and angiogenesis in human glioblastoma. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[15]  M. Chopp,et al.  Stromal Cell-Derived Factor 1α Mediates Neural Progenitor Cell Motility after Focal Cerebral Ischemia , 2006 .

[16]  Michael Chopp,et al.  Magnetic resonance imaging and neurosphere therapy of stroke in rat , 2003, Annals of neurology.

[17]  R. Bonavia,et al.  Stromal Cell-derived Factor 1α Stimulates Human Glioblastoma Cell Growth through the Activation of Both Extracellular Signal-regulated Kinases 1/2 and Akt , 2003 .

[18]  M Chopp,et al.  VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. , 2000, The Journal of clinical investigation.