title: Imaging neural stem cell graft-induced structural repair in stroke.
abstract: Stem cell therapy ameliorates motor deficits in experimental stroke model. Multimodal molecular imaging enables real-time longitudinal monitoring of infarct location, size, and transplant survival. In the present study, we used magnetic resonance imaging (MRI) and positron emission tomography (PET) to track the infarct evolution,tissue repair, and the fate of grafted cells. We genetically engineered embryonic stem cell-derived neural stem cells (NSCs) with a triple fusion reporter gene to express monomeric red fluorescence protein and herpes simplex virus-truncated thymidine kinase for multimodal molecular imaging and SPIO labeled for MRI. The infarct size as well as fate and function of grafted cells were tracked in real time for 3 months using MRI and PET. We report that grafted NSCs reduced the infarct size in animals with less than 0.1 cm(3) initial infarct in a dose-dependent manner, while larger stroke was not amenable to such beneficial effects. PET imaging revealed increased metabolic activity in grafted animals and visualized functioning grafted cells in vivo. Immunohistopathological analysis demonstrated that, after a 3-month survival period, grafted NSCs dispersed in the stroke-lesioned parenchyma and differentiated into neurons, astrocytes, and oligodendrocytes. Longitudinal multimodal imaging provides insights into time course dose-dependent interactions between NSC grafts and structural changes in infarcted tissue.
authors.affiliation: Department of Neurosurgery, Stanford Stroke Center and Stanford Institute for Neuro-Innovationand Translational Neurosciences, Stanford, CA, USA. mdaadi@stanford.edu
authors.forename: Marcel M
authors.initials: MM
authors.lastname: Daadi
authors.forename: Shijun
authors.initials: S
authors.lastname: Hu
authors.forename: Jill
authors.initials: J
authors.lastname: Klausner
authors.forename: Zongjin
authors.initials: Z
authors.lastname: Li
authors.forename: Marc
authors.initials: M
authors.lastname: Sofilos
authors.forename: Guohua
authors.initials: G
authors.lastname: Sun
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu
authors.forename: Gary K
authors.initials: GK
authors.lastname: Steinberg
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D058953:Neural Stem Cells / Q000166:cytology* / Q000637:transplantation; D049268:Positron-Emission Tomography; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D014183:Transplantation, Heterologous
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide; D011505:Protein-Tyrosine Kinases