Genetically modified adipose tissue-derived stem/stromal cells, using simian immunodeficiency virus-based lentiviral vectors, in the treatment of hemophilia B

Hemophilia is an X-linked bleeding disorder, and patients with hemophilia are deficient in a biologically active coagulation factor. This study was designed to combine the efficiency of lentiviral vector transduction techniques with murine adipose tissue-derived stem/stromal cells (mADSCs) as a new...

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Bibliographic Details
Published inHuman gene therapy Vol. 24; no. 3; p. 283
Main Authors Watanabe, Natsumi, Ohashi, Kazuo, Tatsumi, Kohei, Utoh, Rie, Shim, In Kyong, Kanegae, Kazuko, Kashiwakura, Yuji, Ohmori, Tsukasa, Sakata, Yoichi, Inoue, Makoto, Hasegawa, Mamoru, Okano, Teruo
Format Journal Article
LanguageEnglish
Published United States 01.03.2013
Subjects
Adipose Tissue - cytology
Animals
Blood Coagulation
Factor IX - biosynthesis
Factor IX - genetics
Gene Order
Genetic Therapy
Genetic Vectors - genetics
Hemophilia B - blood
Hemophilia B - genetics
Hemophilia B - therapy
Humans
Male
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - metabolism
Mesenchymal Stromal Cells - ultrastructure
Mice
Simian Immunodeficiency Virus - genetics
Transduction, Genetic
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ISSN1557-7422
DOI10.1089/hum.2012.162

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Summary:Hemophilia is an X-linked bleeding disorder, and patients with hemophilia are deficient in a biologically active coagulation factor. This study was designed to combine the efficiency of lentiviral vector transduction techniques with murine adipose tissue-derived stem/stromal cells (mADSCs) as a new method to produce secreted human coagulation factor IX (hFIX) and to treat hemophilia B. mADSCs were transduced with simian immunodeficiency virus (SIV)-hFIX lentiviral vector at multiplicities of infection (MOIs) from 1 to 60, and the most effective dose was at an MOI of 10, as determined by hFIX production. hFIX protein secretion persisted over the 28-day experimental period. Cell sheets composed of lentiviral vector-transduced mADSCs were engineered to further enhance the usefulness of these cells for future therapeutic applications in transplantation modalities. These experiments demonstrated that genetically transduced ADSCs may become a valuable cell source for establishing cell-based gene therapies for plasma protein deficiencies, such as hemophilia.
ISSN:1557-7422
DOI:10.1089/hum.2012.162