Co-Culture Studies To Decode 'Biological PINs' And Exosomes

By Takeo Shimasaki, Ginrei Lab Inc.

Recently, it has become evident that extracellular vesicles, including exosomes, play a major role in the communication of various cells in biology. As such, there has been a dramatic increase in the number of articles on this topic. The current mainstream of exosome research is a method for extracting and analyzing exosomes thought to be related to various diseases and is one of the methods expressed as Liquid Biopsy. However, exosomes are key players in cell-cell interactions, and to truly analyze the functions and disease characteristics of cells via exosomes, apart from a physical fitness measurement-like study where exosomes are extracted and analyzed, it is necessary to perform an interaction study where a phenomenon that occurs in vivo, as in a practice match, is reproduced even in vitro.

This is because, fundamental studies aimed at functional analysis related to exosomes are, broadly speaking, commonly those where, for example, an exosome extracted from cancer cells is administered to other cells, and the behavior of those cells is then observed and analyzed. Then, the functions of that exosome are discussed, followed by the analysis of the inclusions present in that exosome. The functions of the inclusions are further analyzed using molecular biology procedures. The merit of such a method is simply a basic functional analysis, and in case of a machine, one simply pushes the switch and observes what happens. But such a research method is simply pressing a switch, and does the same thing happen in a living organism when a large amount of extracted exosomes is administered? In other words, it is not clear whether such a strong switch is being pressed. Moreover, this study method has a 'security code-like system' (Figure 1) present in the living body, and when the strength, order, etc., are strongly related, it becomes absolutely useless.

The details have been omitted as we plan to publish this article; however, we have confirmed that a 'biological PIN-like system' does exist in the living body. A study where an exosome is extracted and administered to other cells is useful for analyzing the function of a single switch. Henceforth also, there will be no change in the fact that it is a basic analysis method. However, co-culture studies that enable observation of spontaneous interactions between cells without involving extraction techniques are useful for analyzing 'biological PINs.' Although many studies using the co-culture technique have been conducted to date, relatively few studies on exosomes currently use that technique. The use of the co-culture technique is important for analyzing the essential interactions of exosomes. For detailed explanations on exosomes, one can read many reviews on them. This article explains the caution points in exosome study procedures and the co-culture system as an explanatory tool for the purpose of decoding the code numbers in the living body.