title: Consideration of the cellular microenvironment: physiologically relevant co-culture systems in drug discovery.
abstract: There is renewed interest in phenotypic approaches to drug discovery, using cell-based assays to select new drugs, with the goal of improving pharmaceutical success. Assays that are more predictive of human biology can help researchers achieve this goal. Primary cells are more physiologically relevant to human biology and advances are being made in methods to expand the available cell types and improve the potential clinical translation of these assays through the use of co-cultures or three-dimensional (3D) technologies. Of particular interest are assays that may be suitable for industrial scale drug discovery. Here we review the use of primary human cells and co-cultures in drug discovery and describe the characteristics of co-culture models for inflammation biology (BioMAP systems), neo-vascularization and tumor microenvironments. Finally we briefly describe technical trends that may enable and impact the development of physiologically relevant co-culture assays in the near future.
authors: BioSeek, a division of DiscoveRx Corporation, 310 Utah Ave., Suite 100, South San Francisco, CA 94080, USA. Electronic address: eberg@bioseekinc.com.
authors: Ellen
authors: E
authors: L Berg
authors: Departments of Quantitative and Structural Biology, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Drop Code 0703, Indianapolis, IN 46285, USA.
authors: Yu-Chih
authors: YC
authors: Hsu
authors: Departments of Quantitative and Structural Biology, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Drop Code 0703, Indianapolis, IN 46285, USA. Electronic address: jonathan_a_lee@lilly.com.
authors: Jonathan A
authors: JA
authors: Lee
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods* / Q000639:trends; D060833:Cellular Microenvironment / Q000187:drug effects / Q000502:physiology*; D018920:Coculture Techniques / Q000379:methods / Q000639:trends; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D006801:Humans
keywords: Angiogenesis; Assay development; Cell-based assays; Drug discovery; High throughput screening; Inflammation; Lead generation; Primary cells