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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2259-2268. Prepublished online as a Blood First Edition Paper on June 7, 2005; DOI 10.1182/blood-2005-03-1189. This Article Full Text (PDF) Supplemental Table and Figure All Versions of this Article: 2005-03-1189v1 106/7/2259    most recent 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sano, R. Articles by d'Azzo, A. Search for Related Content PubMed PubMed Citation Articles by Sano, R. Articles by d'Azzo, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 24, 2005 Accepted May 23, 2005 Chemokine-induced recruitment of genetically modified bone marrow cells into the CNS of GM1-gangliosidosis mice corrects neuronal pathology Renata Sano, Alessandra Tessitore, Angela Ingrassia, and Alessandra d'Azzo* Department of Genetics and Tumor Cell Biology, St Jude Children's Research Hospital, Memphis, TN, USA * Corresponding author; email: alessandra.dazzo{at}stjude.org. Bone marrow cells (BMCs) could correct some pathologic conditions of the central nervous system (CNS) if these cells would effectively repopulate the brain. One such condition is GM1-gangliosidosis, a neurodegenerative glycosphingolipidosis due to deficiency of lysosomal -galactosidase (-gal). In this disease, abnormal build up of GM1-ganglioside in the endoplasmic reticulum of brain cells results in calcium unbalance, induction of an unfolded protein response, and neuronal apoptosis. These processes are accompanied by the activation/proliferation of microglia and the production of inflammatory cytokines. Here we demonstrate that local neuroinflammation promotes the selective activation of chemokines, such as SDF-1, MIP-1 and MIP-1, which chemoattract genetically modified BMCs into the CNS. Bone marrow transplanted mice showed increased -gal activity in different brain regions and reduced lysosomal storage. Decreased production of chemokines and effectors of unfolded protein response as well as restoration of neurologic functions accompanied this phenotypic reversion. Our results suggest that -gal-expressing BM-derived cells selectively migrate to the CNS under a gradient of chemokines and become a source of correcting enzyme to deficient neurons. Thus, a disease condition like GM1-gangliosidosis, which is characterized by neurodegeneration and neuroinflammation, may influence the response of the CNS to ex vivo gene therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. L. Zozulya, E. Reinke, D. C. Baiu, J. Karman, M. Sandor, and Z. Fabry Dendritic Cell Transmigration through Brain Microvessel Endothelium Is Regulated by MIP-1{alpha} Chemokine and Matrix Metalloproteinases J. Immunol., January 1, 2007; 178(1): 520 - 529. [Abstract] [Full Text] [PDF]

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