Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/328
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dc.contributor.authorMukhopadhyay, Asok-
dc.date.accessioned2014-12-11T07:15:50Z-
dc.date.available2014-12-11T07:15:50Z-
dc.date.issued2009-11-
dc.identifier.urihttp://hdl.handle.net/123456789/328-
dc.description.abstractThe 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.en_US
dc.publisherAmerican Society of Hematologyen_US
dc.titleThe therapeutic effect of bone marrow-derived liver cells in the phenotypic correction of murine hemophilia Aen_US
dc.contributor.coauthorSaxena, Renu-
dc.contributor.coauthorHalder, Ashutosh-
dc.contributor.coauthorJain, Manish-
dc.contributor.coauthorKumar, Suresh-
dc.contributor.coauthorKanjirakkuzhiyil, Sumod-
dc.contributor.coauthorYadav, Neelam-
dc.journalBlooden_US
dc.volumeno114en_US
dc.issueno20en_US
dc.pages4552-4561en_US
Appears in Collections:Stem Cell Biology, Publications

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