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Phenotypic Correction Of Murine Hemophilia A By Bone Marrow- Derived Liver Cells | 5190
ISSN: 2157-7013

Journal of Cell Science & Therapy
Open Access

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Phenotypic correction of murine hemophilia a by bone marrow- derived liver cells

International Conference & Exhibition on Cell Science & Stem Cell Research

Neelam Yadav, Sumod K, Taposh K. Das and Asok Mukhopadhyay

ScientificTracks Abstracts: J Cell Sci Ther

DOI: 10.4172/2157-7013.S1.02

Hemophilia A is caused by mutations within the Factor VIII (FVIII) gene that lead to depleted protein production and ineffi cient blood clotting.Current therapies include fi xed-dose FVIII prophylaxis, factor replacement therapies, and most recently, gene therapy. Liver is the primary site of FVIII synthesis; however, the specifi c cell type(s) responsible for its synthesis remain controversial. We hypothesize that the partial replacement of mutated liver cells by healthy cells in hemophilia A (HA) mice could ameliorate the severity of the bleeding disorder. Th e aim of this investigation was to study the cellular origin of FVIII by examining bone marrow cell (BMCs) therapy for treatment of HA in mice. Recipient liver was perturbed with either acetaminophen or monocrotaline (MCT) to facilitate the engraft ment and diff erentiation of lineage-depleted (Lin-) enhanced green fl uorescent protein (eGFP)-expressing BMCs. Immunohistochemistry experiments with the liv er tissue showed that the donor-derived cells expressed the markers of both hepatocytes (albumin and cytokeratin-18) and endothelial cells (von Willbrand factor). Both cell types expressed FVIII light chain mRNA and protein, which was further confi rmed by transmission electron microscopy. Th e transplanted HA mice showed FVIII activity in plasma ( P < 0.01) and survived tail-clip challenge ( P < 0.001).Th e results of fl uorescent in situ hybridization and immunocytochemistry experiments suggested that diff erentiation was direct in this model. Overall, this report demonstrate that phenotypic correction in HA mice with conditioned liver is possible by transplantation of BMCs. Th us, BMC therapy is a potential alternative approach to managing HA
Dr. Neelam Yadav has completed her Ph.D from Industrial Toxicology Research Centre, Lucknow and postdoctoral studies from Stem Cell Biology Laboratory of National Institute of Immunology (NII) New delhi, India. She is Assistant Professor in Department of Biochemistry, at Dr. R.M.L. Avadh University, Faizabad, India. Dr. Neelam has published many papers in reputed international journals and fi led one patent
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