title: Noninvasive detection of neural progenitor cells in living brains by MRI.
abstract: The presence of pericytes in brain regions undergoing repair is evident of the recruitment of bone marrow-derived multipotent regenerative cells to the neurovascular unit during angiogenesis. At present, post mortem sampling is the only way to identify them. Therefore, such cell typing is inadequate for preserving neural progenitor cells for any meaningful stem cell therapy. We aimed to target cerebral pericytes in vivo using dual gene transcript-targeted MRI (GT-tMRI) in male C57black6 mice after a 60-min bilateral carotid artery occlusion (BCAO). We attached superparamagnetic iron oxide nanoparticles (SPIONs) to phosphorothioate-modified micro-DNA that targets actin or nestin mRNA. Because BCAO compromises the blood-brain barrier (BBB) and induces expression of α-smooth muscle (αSM)-actin and nestin antigens by pericytes in new vessels, we delivered pericyte-specific magnetic resonance contrast agents (SPION-actin or SPION-nestin at 4 mg Fe/kg) by i.p. injection to C57black6 mice that had experienced BCAO. We demonstrated that the surge in cerebral iron content by inductively coupled plasma-mass spectrometry matched the increase in the frequency of relaxivity. We also found that SPION-nestin was colocalized in αSM- actin- and nestin-expressing pericytes in BCAO-treated C57black6 or transgenic mice [B6.Cg-Tg(CAG-mRFP1) 1F1Hadj/J, expressing red fluorescent protein by actin promoter]. We identified pericytes in the repair patch in living brains after BCAO with a voxel size of 0.03 mm(3). The presence of electron-dense nanoparticles in vascular pericytes in the region of BBB injury led us to draw the conclusion that GT-tMRI can noninvasively reveal neural progenitor cells during vascularization.
authors.affiliation: A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA.
authors.forename: Christina H
authors.initials: CH
authors.lastname: Liu
authors.forename: Jia Q
authors.initials: JQ
authors.lastname: Ren
authors.forename: Zerong
authors.initials: Z
authors.lastname: You
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Yang
authors.forename: Charng-Ming
authors.initials: CM
authors.lastname: Liu
authors.forename: Ritika
authors.initials: R
authors.lastname: Uppal
authors.forename: Philip K
authors.initials: PK
authors.lastname: Liu
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000648:ultrastructure; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D058953:Neural Stem Cells / Q000166:cytology* / Q000502:physiology*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D020286:Pericytes / Q000166:cytology / Q000378:metabolism
chemical_list: D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D009838:Oligodeoxyribonucleotides