Open AccessAdhesion and incorporation of lacZ-transduced endothelial cells into the intact capillary wall in the rat.
Author(s) -
Louis M. Messina,
Rachel M. Podrazik,
Thomas A. Whitehill,
Daryoush Ekhterae,
James M. Wilson,
William E. Burkel,
James C. Stanley
Publication year - 1992
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.89.24.12018
Subject(s) - endothelial stem cell , endothelium , skeletal muscle , in vivo , microbiology and biotechnology , ex vivo , somatic cell , biology , transplantation , genetic enhancement , in vitro , anatomy , medicine , gene , biochemistry , genetics
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.