Published Online
on February 26, 2004

A more recent version of this article appeared on April 1, 2004

This Article Full Text (PDF) All Versions of this Article: 35/4/952    most recent 01.STR.0000120308.21946.5Dv1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, D.-E. Articles by Weissleder, R. Search for Related Content PubMed PubMed Citation Articles by Kim, D.-E. Articles by Weissleder, R. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Stem Cells Related Collections Acute Cerebral Infarction Other imaging Other Stroke Treatment - Medical

Submitted on November 14, 2003
Accepted on December 10, 2003

Imaging of Stem Cell Recruitment to Ischemic Infarcts in a Murine Model

Dong-Eog Kim MD; Dawid Schellingerhout MBChB^*; Ken Ishii MD, PhD; Khalid Shah PhD; and Ralph Weissleder MD, PhD

From the Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital, Charlestown, Mass.

^* To whom correspondence should be addressed. E-mail: Dawid{at}helix.mgh.harvard.edu.

Background and Purpose--Neural progenitor cells (NPC) have been reported to aid in the functional recovery from stroke and hold promise as a novel treatment for a variety of neurological diseases. There is a need for imaging tools to study the in vivo migratory behavior of these cells.

Methods--C17.2 NPC, stably transfected with firefly luciferase, were serially imaged through intact skull and skin by bioluminescence imaging over 2 to 3 weeks in nu/nu mice with closed-vessel middle cerebral artery infarcts, followed by contralateral intraparenchymal or intraventricular injections of NPC.

Results--NPC migrated to the site of infarct from the contraleral parenchyma, crossing the midline at 7 days. In control animals without infarcts, NPC remained at the site of administration. Intraventricular cell administration resulted in a wide distribution of cells, including the site of infarct. Within the infarct area, NPC colabeled with the neuronal marker NeuN and with astroglial marker glial fibrillary acidic protein. The time course and magnitude of NPC recruitment were longitudinally compared between the treatment groups.

Conclusions--NPC recruitment to infarct can be assessed noninvasively by serial in vivo imaging. Images correlate well with histological cell distributions. NPC are recruited to infarcts with both parenchymal and cerebrospinal fluid administration, but higher initial photon counts suggest that cerebrospinal fluid administration is more efficient at early infarct seeding.

Key words: diagnostic imaging • infarction • luciferase • stem cells

This article has been cited by other articles:

				P. T. Winnard Jr., A. P. Pathak, S. Dhara, S. Y. Cho, V. Raman, and M. G. Pomper Molecular Imaging of Metastatic Potential J. Nucl. Med., June 1, 2008; 49(Suppl_2): 96S - 112S. [Abstract] [Full Text] [PDF]

				T.F. Massoud, A. Singh, and S.S. Gambhir Noninvasive Molecular Neuroimaging Using Reporter Genes: Part II, Experimental, Current, and Future Applications AJNR Am. J. Neuroradiol., March 1, 2008; 29(3): 409 - 418. [Abstract] [Full Text] [PDF]

				T. Bliss, R. Guzman, M. Daadi, and G. K. Steinberg Cell Transplantation Therapy for Stroke Stroke, February 1, 2007; 38(2): 817 - 826. [Abstract] [Full Text] [PDF]

				D.-E. Kim, K. Tsuji, Y. R. Kim, F.-J. Mueller, H.-S. Eom, E. Y. Snyder, E. H. Lo, R. Weissleder, and D. Schellingerhout Neural Stem Cell Transplant Survival in Brains of Mice: Assessing the Effect of Immunity and Ischemia by using Real-time Bioluminescent Imaging Radiology, December 1, 2006; 241(3): 822 - 830. [Abstract] [Full Text] [PDF]

				J. Luo, A. H. Lin, E. Masliah, and T. Wyss-Coray Bioluminescence imaging of Smad signaling in living mice shows correlation with excitotoxic neurodegeneration PNAS, November 28, 2006; 103(48): 18326 - 18331. [Abstract] [Full Text] [PDF]

				W. S. Sheng, S. Hu, H. T. Ni, T. N. Rowen, J. R. Lokensgard, and P. K. Peterson TNF-{alpha}-induced chemokine production and apoptosis in human neural precursor cells J. Leukoc. Biol., December 1, 2005; 78(6): 1233 - 1241. [Abstract] [Full Text] [PDF]