Tissue-engineered microvascular networks for gene therapy made from adult endothelial and endothelial progenitor cells

Abstract

From their location at the internal surface of blood vessels, endothelial cells may provide a useful site from which to efficiently deliver therapeutic proteins to the circulation. High-passage bovine aortic endothelial cells (BAEC) in Matrigel cultured in vitro remain spherical and decrease in number over time while those mixed with fibroblasts (FB) show improved survival and form interconnected microvascular networks (MVN) in vitro. Inclusion of FB with high-passage, hGH-secreting BAEC in Matrigel prolongs survival and systemic delivery of hGH when gels are implanted subcutaneously in nude mice. The challenge remains to increase and prolong endothelial cell incorporation into blood vessels. Low-passage BAEC alone in Matrigel form MVN and inclusion of fibroblasts potentiates their MVN formation. Endothelial progenitor cells derived from adult human peripheral blood (BOEC) differentiate into endothelial cells while maintaining a large proliferative capacity and may retain their stem-cell characteristics. BOEC suspended in Matrigel and cultured in vitro remain spherical while those mixed with fibroblasts elongate and form interconnected microvascular networks in vitro. Further, BOEC cultured in collagen in the presence of PMA also formed MVN and created lumen-like structures.