Endothelial cell biology and culture methods for drug transport studies

Elena De Angelis, Stephen H. Moss, Colin W. Pouton

Research output: Contribution to journalReview ArticleResearchpeer-review

8 Citations (Scopus)

Abstract

Significant progress has been made in the isolation and culture of endothelial cells. Large vessel endothelial cell culture is well established, and the diversity of microvascular endothelial cell function is now being explored at the molecular level using primary cultures from individual organs. A variety of tests can be used to identify the purity of cultures, and these methods are discussed. The availability of cell culture models of the endothelium has advanced knowledge of endothelial cell pharmacology and immunological interactions at the molecular level. There is much work still to be done which can be accomplished adequately using traditional monolayer culture techniques. Brain microvascular endothelia can be isolated routinely, to produce a good filter-culture model for transport studies across polarized cell monolayers, though to obtain tight junctions with electrical resistance as low as that found in vivo, it is necessary to grow cells in conditioned medium and/or in the presence of cAMP. These treatments promote formation of tight junctions and the establishment of cytoskeletal components to form a tight monolayer. Brain microvascular endothelial in culture have been used to identify receptor-mediated transport systems for various plasma components at a qualitative level. The routine primary culture of microvascular endothelia from peripheral sites is often more difficult and labour intensive. The way forward for transport studies is likely to be establishment of immortalized lines, and development of strict protocols for growth, characterization and preparation of monolayers for transport studies. The long-term aims of correlating transport in vitro with transport in vivo, and subsequently using cell culture models to predict the nature of microvascular endothelial transport in vivo, require models of well-established validity. The technology of isolation, culture and characterization of endothelia needs to go through a period of considerable development and maturation before these long-term aims will become a realistic prospect.

Original languageEnglish
Pages (from-to)193-218
Number of pages26
JournalAdvanced Drug Delivery Reviews
Volume18
Issue number2
DOIs
Publication statusPublished - 15 Jan 1996

Keywords

  • Characterization
  • Endocytosis
  • Filter culture
  • Immortalization
  • Isolation
  • Microvascular endothelium
  • Primary culture
  • Receptor-mediated transport
  • Separation
  • Transcytosis

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