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 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.
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan.
Natsumi
N
Watanabe
Kazuo
K
Ohashi
Kohei
K
Tatsumi
Rie
R
Utoh
In Kyong
IK
Shim
Kazuko
K
Kanegae
Yuji
Y
Kashiwakura
Tsukasa
T
Ohmori
Yoichi
Y
Sakata
Makoto
M
Inoue
Mamoru
M
Hasegawa
Teruo
T
Okano
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001777:Blood Coagulation; D005164:Factor IX / Q000096:biosynthesis / Q000235:genetics; D023061:Gene Order; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D002836:Hemophilia B / Q000097:blood / Q000235:genetics* / Q000628:therapy*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D014161:Transduction, Genetic
D005164:Factor IX