The Rise of Physiologic Media

Abstract

Developed decades ago, traditional culture media were not intended to resemble the metabolic composition of human blood, and indeed poorly do so. Yet, despite what is now a clear recognition that environmental factors influence metabolism, such media remain standard to in vitro studies across virtually all areas of biological research. The recent development of physiologic media, like other efforts designed to address the modeling capacity of cell culture, holds immense potential to improve understanding and interpretation of diverse biological and pharmacological studies.

Figure 1.. Summary of Controlled Cell Culture Conditions and Recent Efforts to Address the Modeling Capacity of in vitro Systems.

Cell culture provides an artificial environment of controlled biochemical, mechanical, physical, and physicochemical conditions that influence metabolism and other cellular processes. Airtight chambers can permit cell culture under more physiologically relevant oxygen tension levels (A), 3D organoids are intended to recapitulate tissue architecture (B), and various co-culture methods and organ-on-a-chip systems may better mimic possible interactions between different cell types or tissues/organs, respectively (C). However, there has been relatively less consideration for improving the modeling capacity of in vitro biochemical conditions, which are still primarily dictated by classic media that were developed generations ago (D).

Figure 2.. Overview of Relative Basal Media Compositions.

(A) Heatmap depicting relative concentrations of defined basal media components compared to those in adult human plasma (log₂-transformed fold changes). Components not present in a medium are marked as absent. Values used to generate the heatmap are defined elsewhere [42]. *RPMI further contains vitamin B12 (3.69 nM). (B) Additional HPLM components that are absent from the defined formulations of basal media described in panel (A). Designations used to group metabolites are not intended to be exclusive. *RPMI contains 4-Hydroxyproline at a concentration (153 μM) nearly eightfold that defined in HPLM. Abbreviations: BME, Basal Medium Eagle; DMEM, Dulbecco’s Modified Eagle Medium; HPLM, human plasma-like medium; MEM, Minimal Essential Medium; RPMI, Roswell Park Memorial Institute; denotes RPMI 1640.