Transplantation of Murine Bone Marrow Stromal Cells under the Kidney Capsule to Secrete Coagulation Factor VIII

Cell Transplantation

Article

Alexandra Peister¹  Frank Park²  Taekeun Oh³  Kazuo Ohashi⁴ 

[1] Department of Biochemistry, Tulane University, New Orleans, LA, USA;Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA;Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA; Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, South Korea.;First Department of Surgery, Nara Medical University, Nara, Japan;

关键词: Lentiviral vectors;    Bone marrow stromal cells;    Human factor VIII;    Ectopic transplantation;    Kidney capsule;   

DOI  :  10.3727/000000006783981620

 received in 2005-12-13, accepted in 2006-05-30,  发布年份 2006

来源: Sage Journals

【 摘 要 】

Ectopic cell transplantation has been studied as an alternative to whole organ transplantation or as a method to produce secretable proteins for genetic disorders. In this study, bone marrow stromal cells isolated from C57Bl/6 mice were genetically modified to express either lacZ- or B-domain-deleted human factor VIII. In vitro modification of the isolated bone marrow stromal cells was initially performed by transducing increased doses of VSV-G pseudotyped lentiviral vectors expressing lacZ. At a MOI of 25, all of the bone marrow stromal cells were X-gal positive, which maintained their ability to expand and differentiate prior to transplantation into mice. Extremely poor engraftment was observed in the liver, but transplantation of the bone marrow stromal cells expressing lacZ under the kidney capsule resulted in long-term viable X-gal-positive cells for at least 8 weeks (length of study). In vitro expression of human factor VIII was detected in a dose-dependent manner following bone marrow stromal cell with a factor VIII-expressing lentiviral vector. Transplantation of the factor VIII-expressing bone marrow stromal cells under the kidney capsule led to long-term therapeutic expression in the mouse plasma (1–3 ng/ml; n = 4–5 mice/group) for 8 weeks. This study demonstrated that ectopic transplantation of bone marrow stromal cells under the kidney capsule can be effective as a method to express secretable proteins in vivo.

【 授权许可】

Unknown   
© 2006 Cognizant Comm. Corp.