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.

Optimization of Organotypic Cultures of Mouse Spleen for Staining and Functional Assays

“…Organotypic culture has emerged as a powerful technique which allows the analysis of tissue behavior in a variety of conditions. Initially developed as an alternative to classical 2-D in vitro culture of neurons, slices obtained by sectioning the brain region of interest with tissue choppers allowed to maintain neurons alive outside of the body and were found to be suitable for electrophysiological studies (1). Preparation and in vitro growth of these slices were progressively optimized to be maintained in culture for several days thanks to the introduction of modern tissue choppers such as vibrating microtomes, that produce thinner and less damaged slices, and tissue support systems, such as agarose, to preserve the 3-D organization of the tissue (1,2).…”

“…Organotypic culture has been extended to several other organs of the neuroendocrine system (1) and, more recently, to tumor-derived tissues (3). Of note, only one report describes the application of this technique to lymphoid tissues of human origin (4), notwithstanding the wealth of information generated over the last decade on the complex interactions that occur among immune, stromal, and cancer cells (5,6).…”

Why Study the History of Neuroscience?

“…Your experimental methods, both those explicitly referenced in the article and those tacitly passed on, all have a history. In some cases, older methods may be used to solve research problems in the present (Schwerdtfeger, 2018; Schwerdtfeger and Tobet, 2018). The core of your research article is the presentation of new results.…”

Vasoactive intestinal peptide regulates ileal goblet cell production in mice

“…This is partially due to investigations using monolayer epithelial culture models that until recently did not contain a mucus layer (Wang, Kim, Sims, & Allbritton, ). While this is an advance, epithelial culture systems miss the cellular diversity of the gut wall, a critical aspect of in vivo physiologic function (McLean, Schwerdtfeger, Tobet, & Henry, ; Schwerdtfeger & Tobet, ). Understanding intestinal wall function ultimately requires parsing the interactions of the diverse cellular elements.…”