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Review
. 2020 Sep 17;7(3):115.
doi: 10.3390/bioengineering7030115.

Innovative Human Three-Dimensional Tissue-Engineered Models as an Alternative to Animal Testing

Patrick Bédard  1   2 , Sara Gauvin  1   2 , Karel Ferland  1   2 , Christophe Caneparo  2 , Ève Pellerin  2 , Stéphane Chabaud  2 , Stéphane Bolduc  2   3
Affiliations
Review

Innovative Human Three-Dimensional Tissue-Engineered Models as an Alternative to Animal Testing

Patrick Bédard et al. Bioengineering (Basel). .

Abstract

Animal testing has long been used in science to study complex biological phenomena that cannot be investigated using two-dimensional cell cultures in plastic dishes. With time, it appeared that more differences could exist between animal models and even more when translated to human patients. Innovative models became essential to develop more accurate knowledge. Tissue engineering provides some of those models, but it mostly relies on the use of prefabricated scaffolds on which cells are seeded. The self-assembly protocol has recently produced organ-specific human-derived three-dimensional models without the need for exogenous material. This strategy will help to achieve the 3R principles.

Keywords: epithelium; extracellular matrix; scaffold; tissue engineering.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Advantages and applications of common animal models: drosophila [7], zebrafish [8], Xenopus [9], rabbit [10], or rodent [11] models in biomedical research.
Figure 2
Figure 2
Number of Pubmed indexed publications on different animal models. The number of publications is the number obtained when entering the keyword in the search bar on PubMed website.
Figure 3
Figure 3
Number of publications per year about 3D cell culture on Pubmed since 1968. The number of publications is the number obtained when entering the keyword “3D cell cultures” in the search bar and applying the filter of results by year on Pubmed website.
Figure 4
Figure 4
Schematic description of the tissue strands technique based on the ability of the cells to self-assemble into a tissue. Sodium alginate and a crosslinker solution are used to form tubular alginate capsules with a coaxial nozzle into a cell culture dish. Once polymerized, the capsules are filled with a cell pellet, and their ends are tightly sealed with vessel clips. After a 5–7 day culture, a sodium citrate solution is added to depolymerize the capsules, leaving complete and dense tissue strands that can later be used as building blocks to form complex larger tissues [186].
Figure 5
Figure 5
Scaffold vs. scaffold-free 3D cell culture.
Figure 6
Figure 6
Schematic description of the basic and the reseeding self-assembly techniques used in Tissue Engineering. For the basic self-assembly technique, mesenchymal cells are seeded into three cell culture dishes containing a paper anchor and rust-resistant light metal weights at the bottom. After 28 days in culture with ascorbate, the stromal sheets formed are stacked upon each other for a variable time with a mechanical load composed of a surgical sponge and rust-resistant heavy metal ingots and with surgical Ligaclips to ensure the fusion of the sheets. Epithelial cells are seeded on top of the construct, and the culture is continued for seven more days. After that, tissues are mounted onto supports and maintained at the air/liquid interface for 21 consecutive days to ensure a complete maturation of the epithelium. The first step for the reseeding self-assembly technique is similar to the one for the classic self-assembly technique. However, instead of stacking the stroma sheets later, mesenchymal cells are reseeded on top of the stroma sheets after 14 days of culture with ascorbate. Fourteen days later, epithelial cells are seeded on top of the stroma sheets, and the culture is continued for an additional seven days. The tissue constructs are then maintained at the air/liquid interface with support for 21 days to ensure a complete maturation of the epithelium [108].
Figure 7
Figure 7
Types of tissues that can be reconstructed by tissue engineering using the self-assembly technique developed at LOEX.
See this image and copyright information in PMC

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