Adhesion and Incorporation of lacZ-Transduced Endothelial Cells into the Intact Capillary Wall in the Rat

Use of the capillary bed of skeletal muscle as an in vivo recipient site to transplant autologous endothelial cells that have undergone gene transfer ex vivo has considerable potential as a technique of somatic gene therapy. Here we document a previously unrecognized capacity of endothelial cells to...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1992-12, Vol.89 (24), p.12018-12022
Main Authors: Messina, Louis M., Podrazik, Rachel M., Whitehill, Thomas A., Ekhterae, Daryoush, Brothers, Thomas E., Wilson, James M., Burkel, William E., Stanley, James C.
Format: Article
Language:English
Subjects:
Animals
beta-Galactosidase - genetics
Capillaries
Cell Adhesion
Cell growth
Cell lines
Cells
Cells, Cultured
Cellular biology
Dogs
Endothelial cells
Endothelium
Endothelium, Vascular - cytology
Gene therapy
Genetic Therapy - methods
In Vitro Techniques
Liver
Microscopy, Electron
Rats
Rats, Wistar
Rodents
Skeletal muscle
Transduction, Genetic
Transfection - methods
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Summary:Use of the capillary bed of skeletal muscle as an in vivo recipient site to transplant autologous endothelial cells that have undergone gene transfer ex vivo has considerable potential as a technique of somatic gene therapy. Here we document a previously unrecognized capacity of endothelial cells to adhere and incorporate spontaneously into confluent endothelial cell monolayers in vitro and in vivo. This spontaneous adhesion and incorporation of endothelial cells enabled us to seed lacZ-transduced endothelial cells into the wall of skeletal muscle capillaries of the hindlimb of the rat. Certain transduced endothelial cells became incorporated within the capillary wall, whereas others remained within the capillary lumen where they formed focal, electron-dense, contacts with host endothelium. lacZ expression in the capillary bed was documented for up to 1 month after transplantation. Use of the intact capillary bed of skeletal muscle as an in vivo recipient site for transduced, autologous endothelial cells holds promise as a strategy for somatic gene therapy to treat various genetic and acquired human diseases.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.89.24.12018