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DOI: 10.1160/TH07-09-0559
Successful in vivo propagation of factor IX-producing hepatocytes in mice: Potential for cell-based therapy in haemophilia B
Financial support: This study was supported in part by The Leading Projects (K.O. and T.O.) and Grant-in- Aid (no. 18591957 to K.O.) from the Scientific Research from the Ministry of Education, Science, Sport and Culture of Japan, grants for AIDS Research from the Ministry of Health, Labor and Welfare of Japan (A.Y.), and grant for CLUSTER (K.Y.).Publikationsverlauf
Received 12. September 2007
Accepted after major revision 12. März 2008
Publikationsdatum:
30. November 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200805/lookinside/thumbnails/10-1160-th07-09-0559-1.jpg)
Summary
Cell-based therapies using isolated hepatocytes have been proposed to be an attractive application in the treatment of haemophilia B due to the normal production of coagulation factor IX (FIX) in these particular cells. Current cell culture technologies have largely failed to provide adequate isolated hepatocytes, so the present studies were designed to examine a new approach to efficiently proliferate hepatocytes that can retain normal biological function, including the ability to synthesize coagulation factors like FIX. Canine or human primary hepatocytes were transplanted into urokinase-type plasminogen activatorsevere combined immunodeficiency (uPA/SCID) transgenic mice. Both donor hepatocytes from canines and humans were found to progressively proliferate in the recipient mouse livers as evidenced by a sharp increase in the circulating blood levels of species-specific albumin, which was correlated with the production and release of canine and human FIX antigen levels into the plasma. Histological examination confirmed that the transplanted canine and human hepatocytes were able to proliferate and occupy >80% of the host livers. In addition, the transplanted hepatocytes demonstrated strong cytoplasmic staining for human FIX, and the secreted coagulation factor IX was found to be haemostatically competent using specific procoagulant assays. In all, the results from the present study indicated that developments based on this technology could provide sufficient FIX-producing hepatocytes for cell-based therapy for haemophilia B.
# Present address: PhoenixBio Co. Ltd, Hiroshima, Japan.
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