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Organotypic culture: from the beginning to 3D cell culture

What is the organotypic culture

Figure 1: Illustration of various organotypic culture method.

Organotypic culture is defined as the culture of an organ collected from an organism. It is one method allowing the culture of complex tissues or organs. Organotypic culture allows the preservation of the architecture of the cultured organ and most of its cellular interactions.

Several protocols have already been developed for the organotypic culture like agar methods, watch glass protocols, organ culture in media, and filter well inserts.


Historical background

Figure 2: Time scale of the parallel development of both organotypic culture and cell lines

While cells lines are one of the most often used experimental model by scientists, surprisingly, culture of whole organs start few decades before the first establishment of cell lines.

At the end of the 19th century, L. Loeb managed to cultivated organs of rabbit. Quickly after, other authors report the culture of different organs collected from different organisms. In the meantime, the first establishment of cell lines has been done, slowing the development of organotypic culture. The HeLa cell line marked the beginning of the intensive utilization of such a system by the scientific community. For example, HeLa cells are now cited in more than 70000 articles and part of 11000 patents. MCF-7 cells (another classically used cell line) are cited in more than 23000 articles. It reflects the intensive use of cell lines in research.


Assets and drawbacks of organotypic cultures

Figure 3: Schematic view of features for different culture model: from fractions to organotypic culture

The massive use of cell line by researchers comes from the need to have a robust, reproducible, cheap and fast experimental model, that are key features of cell line cultures. Despite all of these advantages, some drawbacks appear over time. First, the genetic deviation/differences of cells from the same cell line between two samples lead to the loss of reproducibility and robustness while using cell lines as models. Second is the loss of certain cell functions because the culture conditions are driven by the growth and not by the expression of a tissue-like phenotype. An illustration of this is the metabolism in the liver and liver cell lines. This bias makes the extrapolation of cell lines data to human tricky or even unrealistic.

Since few years, the pressure of regulation agencies to improve the risk assessment for humans has lead to re-consider the use of organotypic cultures. Whereas they are more expensive, more complex and time-consuming, they offer better extrapolation possibilities and are more relevant by taking into account the physiological environment. One of the best models is the organotypic culture of human organs, but the difficulties to handle such a system and to obtain such organs push researchers towards new systems offering both the advantages of cell cultures and organs culture.


 

From organotypic culture to 3D models

Figure 4: A: representation of the derivation of human cell cultures to obtain human spheroids ; B: synergy and inter-dependency of different cultures approaches. From Pamies and Hartun, 21st century cell culture for 21st century toxicology, Chemical Researchin toxicology, 2016.

As mentioned above, there is now a need for developing new in vitro systems offering the advantages of both cell lines and organ culture. One of the solutions is the 3D cell cultures, eg. spheroids. The development of such a technique has to be based on the knowledge acquired with the two models. For more details on spheroïds, you can refer to this page.


Bibliography/Sources

Figure 4: Pamies and Hartun, 21st century cell culture for 21st century toxicology, Chemical Researchin toxicology, 2016.

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Written by Pierre Gaudriault

Written by Pierre Gaudriault

Innovation Unit | Intrapreneur

Pierre is incubated in our Entrepreneurship school. LEARN MORE.
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