Transplantation of murine bone marrow stromal cells under the kidney capsule to secrete coagulation factor VIII

Taekeun Oh, Alexandra Peister, Kazuo Ohashi, Frank Park

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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 C57B1/6 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.

Original languageEnglish (US)
Pages (from-to)637-645
Number of pages9
JournalCell Transplantation
Volume15
Issue number7
DOIs
StatePublished - Dec 18 2006

Fingerprint

Factor VIII
Coagulation
Mesenchymal Stromal Cells
Capsules
Bone
Transplantation
Kidney
Human engineering
Cells
Transplantation (surgical)
Proteins
Inborn Genetic Diseases
Cell Transplantation
Organ Transplantation
Liver
Liver Transplantation
Plasmas

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Transplantation

Cite this

Transplantation of murine bone marrow stromal cells under the kidney capsule to secrete coagulation factor VIII. / Oh, Taekeun; Peister, Alexandra; Ohashi, Kazuo; Park, Frank.

In: Cell Transplantation, Vol. 15, No. 7, 18.12.2006, p. 637-645.

Research output: Contribution to journalArticle

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