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Blood, 8 October 2009, Vol. 114, No. 15, pp. 3181-3190. Prepublished online as a Blood First Edition Paper on July 8, 2009; DOI 10.1182/blood-2009-02-205708. This Article Full Text (PDF) Supplemental Methods, Table, and Figure All Versions of this Article: blood-2009-02-205708v1 114/15/3181    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 Google Scholar Articles by Campeau, P. M. Articles by Galipeau, J. PubMed PubMed Citation Articles by Campeau, P. M. Articles by Galipeau, J. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 17, 2009 Accepted June 24, 2009 Characterization of Gaucher disease bone marrow mesenchymal stromal cells reveals an altered inflammatory secretome Philippe M. Campeau, Moutih Rafei, Marie-Noelle Boivin, Ying Sun, Gregory A. Grabowski, and Jacques Galipeau* The Montreal Center for Experimental Therapeutics in Cancer, Lady Davis Institute for Medical Research, Montreal, QC, Canada Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States Department of Human Genetics, McGill University, Montreal, QC, Canada * Corresponding author; email: jacques.galipeau{at}mcgill.ca. Gaucher disease causes pathological skeletal changes which are not fully explained. Considering the important role of mesenchymal stromal cells (MSCs) in bone structural development and maintenance, we analyzed the cellular biochemistry of MSCs from an adult patient with Gaucher disease type 1 (N370S/L444P mutations). Gaucher MSCs possessed a low glucocerebrosidase activity and consequently had a 3-fold increase in cellular glucosylceramide. Gaucher MSCs have a typical MSC marker phenotype, normal osteocytic and adipocytic differentiation, growth, exogenous lactosylceramide trafficking, cholesterol content, lysosomal morphology and total lysosomal content, and a marked increase in COX-2, prostaglandin E2, IL-8 and CCL2 production when compared to normal controls. Transcriptome analysis on normal MSCs treated with the glucocerebrosidase inhibitor conduritol B epoxide revealed an upregulation of an array of inflammatory mediators, including CCL2, and other differentially regulated pathways. These cells also demonstrated a decrease in sphingosine-1-phosphate. In conclusion, Gaucher disease MSCs display an altered secretome which could contribute to skeletal disease and immune disease manifestations in a manner distinct and additive to Gaucher macrophages themselves. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Mesenchymal gaucho homing on the range Neal J. Weinreb Blood 2009 114: 3134-3135. [Abstract] [Full Text] [PDF] This article has been cited by other articles: N. J. Weinreb Mesenchymal gaucho homing on the range Blood, October 8, 2009; 114(15): 3134 - 3135. [Abstract] [Full Text] [PDF]

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