Directed endothelial differentiation of cultured embryonic yolk sac cells in vivo provides a novel cell-based system for gene therapy.
Cultured murine yolk sac cells transfected with the cytomegalovirus immediate early promoter/human growth hormone (CMVIE-hGH) fusion gene, expressing high levels of hGH in culture, and suspended in Matrigel were subcutaneously (s.c.) injected into experimental mice. The injected cells were shown to form discrete vesicular structures within the Matrigel implant, suggesting directed differentiation of the embryonic yolk sac cells into endothelial tissue. Human growth hormone radioimmune assay of these mice showed sustained physiologically significant levels of hGH in their serum for beyond four months. These results confirmed that long-term cultured murine embryonic yolk sac cells can be induced to differentiate into endothelial cells both in vivo and in vitro and suggested a novel approach to the delivery to the circulation of therapeutic proteins for the treatment of inherited and acquired diseases.
Molecular and Cellular Biology Program, Ohio University, Athens 45701, USA.
Y
Y
Wei
T
T
Quertermous
T E
TE
Wagner
D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002454:Cell Differentiation; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics; D004622:Embryo, Mammalian; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005434:Flow Cytometry; D017781:Genes, Immediate-Early; D015316:Genetic Therapy / Q000379:methods*; D013006:Growth Hormone / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011401:Promoter Regions, Genetic; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis; D014162:Transfection; D015017:Yolk Sac / Q000166:cytology* / Q000637:transplantation*
D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011994:Recombinant Proteins; D013006:Growth Hormone