The renaissance of human skin organ culture: A critical reappraisal.

Human skin organ culture (hSOC) is a simple but highly instructive and clinically relevant skin research method. It has been used for decades to study the development, differentiation, and function as well as the response to wounding or test agents of intact human skin in the presence of its appendages and all resident cell populations. hSOC has also proven useful in toxicological and oncological studies and studies of skin aging (both chronological aging and photoaging), skin energy metabolism, skin immunology, pigmentation biology, and cutaneous (neuro-)endocrinology and neurobiology. The pathobiology and treatment of various dermatoses can also be assessed ex vivo by organ-culturing intact lesional human skin. In addition to morphological analyses by routine histochemistry, quantitative (immuno)histomorphometry has proven to be an excellent tool for quantitating and localizing protein expression patterns in defined skin compartments and distinct cell populations using a relatively small amount of precious human tissue. Finally, more recent technological advances, such as siRNA-mediated gene silencing and sensory reinnervation of hSOCs, have further extended the range of methodological applications for the ex vivo study of human skin; it has emerged as the ultimate preclinical assay system for investigative dermatology, including the testing of drugs, cosmeceuticals and nutraceuticals and more, and is just one step below human skin xenotransplant in vivo mouse models and clinical trials. Here, we critically review the renaissance and variety of hSOC assays, their applications and limitations, and we critically compare them with 3D skin "equivalent" assays. The review closes with perspectives on how this ancient but highly informative and physiologically relevant ex vivo skin research method may be further developed in the future.