A new generation organ culture arising from cross-talk between multiple primary human cell types.

The inability to experiment directly on humans strongly constrains biomedical research, creating a great need to develop cultures that mimic human tissues and organs as experimental systems that can be used to directly understand and manipulate biological processes. The advent of availability of primary human cells now makes possible engineering of such organ cultures. Here we report the generation of a human "skin" arguably the simplest human tissue. Beginning with three primary cell types taken from adult tissues, this organ culture develops into a mature tissue containing a stratified epithelium and an interconnected network of mature microvessels, with appropriate matrix molecules and cytokines. Surprisingly, pericytes and monocytes appear adjacent to and within "blood" vessels, respectively. These cultures respond appropriately to stimulators of specific biological processes, providing a vehicle to investigate basic biological processes, such as 1) cell-cell and cell-microenvironment interaction; 2) transdifferentiation of one cell type to another and/or differentiation from stem cells present in adult tissues; and 3) opportunities for genetic manipulation of human tissues to understand function. Moreover, this "skin" can potentially be developed into a tailored "living bandage" for patients with impaired healing and can serve as prototype for the development of other human organ cultures.