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Blood, 12 November 2009, Vol. 114, No. 20, pp. 4552-4561. Prepublished online as a Blood First Edition Paper on September 14, 2009; DOI 10.1182/blood-2009-02-202788. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2009-02-202788v1 114/20/4552    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 CrossRef Google Scholar Articles by Yadav, N. Articles by Mukhopadhyay, A. PubMed PubMed Citation Articles by Yadav, N. Articles by Mukhopadhyay, A. Related Collections Thrombosis and Hemostasis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  THROMBOSIS AND HEMOSTASIS The therapeutic effect of bone marrow–derived liver cells in the phenotypic correction of murine hemophilia A Neelam Yadav1, Sumod Kanjirakkuzhiyil1, Suresh Kumar2, Manish Jain3, Ashutosh Halder3, Renu Saxena2, and Asok Mukhopadhyay1 1 Stem Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg; 2 Hematology Department, All India Institute of Medical Sciences, Ansari Nagar; and 3 Reproductive Biology Department, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India The transdifferentiation of bone marrow cells (BMCs) into hepatocytes has created enormous interest in applying this process to the development of cellular medicine for degenerative and genetic diseases. Because the liver is the primary site of factor VIII (FVIII) synthesis, we hypothesized that the partial replacement of mutated liver cells by healthy cells in hemophilia A mice could manage the severity of the bleeding disorder. We perturbed the host liver with acetaminophen to facilitate the engraftment and hepatic differentiation of lineage-depleted enhanced green fluorescent protein-expressing BMCs. Immunohistochemistry experiments with the liver tissue showed that the donor-derived cells expressed the markers of both hepatocytes (albumin and cytokeratin-18) and endothelial cells (von Willebrand factor). The results of fluorescent in situ hybridization and immunocytochemistry experiments suggested that differentiation was direct in this model. The BMC-recipient mice expressed FVIII protein and survived in a tail clip challenge experiment. Furthermore, a coagulation assay confirmed that the plasma FVIII activity was maintained at 20.4% (± 3.6%) of normal pooled plasma activity for more than a year without forming its inhibitor. Overall, this report demonstrated that BMCs rescued the bleeding phenotype in hemophilia A mice, suggesting a potential therapy for this and other related disorders. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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