From organotypic culture to body-on-a-chip: A neuroendocrine perspective

Abstract

The methods used to study neuroendocrinology have been as diverse as the discoveries to come out of the field. Maintaining live neurones outside of a body in vitro was important from the beginning, building on methods that dated back to at least the first decade of the 20th Century. Neurosecretion defines an essential foundation of neuroendocrinology based on work that began in the 1920s and 1930s. Throughout the first half of the 20th Century, many paradigms arose for studying everything from single neurones to whole organs in vitro. Two of these survived as preeminent systems for use throughout the second half of the century: cell cultures and explant systems. Slice cultures and explants that emerged as organotypic technologies included such neuroendocrine organs such as the brain, pituitary, adrenals and intestine. The vast majority of these studies were carried out in static cultures for which media were changed over a time scale of days. Tissues were used for experimental techniques such as electrical recording of neuronal physiology in single cells and observation by live microscopy. When maintained in vitro, many of these systems only partially capture the in vivo physiology of the organ system of interest, often because of a lack of cellular diversity (eg, neuronal cultures lacking glia). Modern microfluidic methodologies show promise for organ systems, ranging from the reproductive to the gastrointestinal to the brain. Moving forward and striving to understand the mechanisms that drive neuroendocrine signalling centrally and peripherally, there will always be a need to consider the heterogeneous cellular compositions of organs in vivo.