Special review series on 3D organotypic culture models: Introduction and historical perspective

Abstract

Three dimensional (3D) organ-like (organotypic) culture models are a rapidly advancing area of in vitro biological science. In contrast to monolayer cell culture methods which were developed to achieve proliferation of animal cells in the beginning of in vitro biology, the advancements in 3D culture methods are designed to promote cellular differentiation, and to achieve in vivolike 3D structure and organotypic functions. This project was conceived through the Society for In Vitro Biology to draw on the expertise of individual scientists with special expertise in organotypic cultures of selected tissues or associated interrogation methods to prepare individual-focused reviews in this series. This introductory manuscript will review the early achievements of animal cell culture in monolayer culture and the limitations of that approach to reproduce functioning organ systems. Among these are the nature and 3D architecture of the substrate on which or in which the cells are grown, physical and mechanical clues from the substrate, cell-cell interactions, and defined biochemical factors that trigger the induction of the 3D organotypic differentiation. The organoid culture requires a source of cells with proliferative capacity (ranging from tissue-derived stem or immortalized cells to the iPSC cultures), a suitable substrate or matrix with the mechanical and stimulatory properties appropriate for the organotypic construct and the necessary stimulation of the culture to drive differentiation of the cell population to form the functioning organotypic construct. Details for each type of organotypic construct will be provided in the following papers.

Overexpression of miR-124 in Motor Neurons Plays a Key Role in ALS Pathological Processes

“…To assess the effects of the secretomes from the non-treated and anti-miR-124-treated mSOD1 MNs on microglia polarization, microglial cells were isolated from the SC of WT mice pups and maintained for 2 days in vitro (2DIV) after being 21 DIV in mixed glial culture [ 27 ]. To further evaluate the harmful (the first) and beneficial (the second) effects of such secretomes, we used SC organotypic cultures from mSOD1 mice at early symptomatic stage (10–12 weeks-old), which are considered the best way to preserve cell–cell interactions and the biochemical organization of cells in the SC [ 28 , 29 ].…”

Reprogramming of the Genome-Wide DNA Methylation Landscape in Three-Dimensional Cancer Cell Cultures

“…These assumptions are based on recent advances which have shown the extensive reprogramming of the epigenetic landscape due to microenvironmental changes leading to aberrant gene expression patterns that contribute to the malignant progression of cancer. However, despite remarkable advances, further research is required to uncover which is the best cell culture model to reflect every single component of the tumor microenvironment involved in the epigenetic landscape [ 46 , 47 ].…”

A Short History of the Consideration of Sex Differences in Biomedical Research — Lessons for the In Vitro Community from Animal Models and Human Clinical Trials

“…46 In the in vitro community, there is a current trend away from single cell type approaches toward more-complex multi-cell type models (based on primary cells, cell lines or stem cells) in 3-D configurations, microfluidic systems or as self-organising organoids. [47][48][49][50] This trend involves the establishment of cocultured multi-cell models in 3-D configurations and can be applied to many tissue types, including: lung, 51,52 liver, 53 blood-brain barrier 54 or intestine. 55 The added value of such complex models has been shown for the lung, where an unexposed tetraculture model, cultured at the air-liquid interface, 51 showed up to 90% similarity in active gene networks compared with the in vivo situation.…”