Powering ex vivo tissue models in microfluidic systems

Abstract

This Frontiers review analyzes the rapidly growing microfluidic strategies that have been employed in attempts to create physio relevant 'organ-on-chip' models using primary tissue removed from a body (human or animal). Tissue harvested immediately from an organism, and cultured under artificial conditions is referred to as ex vivo tissue. The use of primary (organotypic) tissue offers unique benefits over traditional cell culture experiments, and microfluidic technology can be used to further exploit these advantages. Defining the utility of particular models, determining necessary constituents for acceptable modeling of in vivo physiology, and describing the role of microfluidic systems in tissue modeling processes is paramount to the future of organotypic models ex vivo. Virtually all tissues within the body are characterized by a large diversity of cellular composition, morphology, and blood supply (e.g., nutrient needs including oxygen). Microfluidic technology can provide a means to help maintain tissue in more physiologically relevant environments, for tissue relevant time-frames (e.g., matching the natural rates of cell turnover), and at in vivo oxygen tensions that can be controlled within modern microfluidic culture systems. Models for ex vivo tissues continue to emerge and grow in efficacy as mimics of in vivo physiology. This review addresses developments in microfluidic devices for the study of tissues ex vivo that can serve as an important bridge to translational value.

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

“…Many organotypic culture systems have been 'static' in that they did not perfuse media through the preparations, and required media changes every 1-7 days. 120 In the development of "organs-on-a-chip", most have utilised cultures of immortalised cell lines, often in monolayers. That said, fluid dynamics in those systems were difficult to regulate, shear stresses were not accounted for, and time ex vivo was limited.…”

“…With the explosion of microfluidic technologies in the early 21st Century, it is easier to find organotypic culture systems incorporating constantly perfused microfluidic delivery of media, generating organon-a-chip systems. 120,122 Intestinal research has been at the forefront of recent developments for organ-on-a-chip systems. 120 In the development of "organs-on-a-chip", most have utilised cultures of immortalised cell lines, often in monolayers.…”

“…120 Varied device materials contribute to health of tissue on-chip, and have been reviewed recently. 120 In the development of "organs-on-a-chip", most have utilised cultures of immortalised cell lines, often in monolayers. 115,121 Continuously perfused media provides a more consistent delivery of oxygen and nutrients, and removal of cellular waste products.…”

“…122 An ideal device for culturing organs outside the body would offer this efficient and regular nutrient and oxygen delivery, coupled with access to microscopy and electrophysiological methods. 120,122 Intestinal research has been at the forefront of recent developments for organ-on-a-chip systems. Early gut-on-a-chip devices were caco-2 monolayers cultured with continuous media flow.…”

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.…”