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What is ‘ex vivo’? Differences between ‘in vitro’ and ‘in vivo’



Hello.


Have you heard of the term ‘ex-vivo", recently, alongside in vitro and in vivo?


  • What is ex-vivo in the first place?

  • What's the difference between in vitro and in vivo?


I hope that this article will answer any questions.



Table of contents


  1. Cells take the center stage in ‘in vitro’

  2. In ‘in vivo’ animals are the protagonists

  3. What is ‘ex vivo’? The main role is ‘organs and tissues’

  4. A brief history of ‘in vitro’, ‘in vivo’, and ‘ex vivo’

  5. Lowering the hurdles in ‘ex vivo’ research

  6. Summary




Cells take center stage in ‘in vitro’



In vitro is a Latin term which means "in the test tube", and I think that the in vitro test, used during in vitro research, and the word ‘vitro’, itself, have taken over the minds of Japanese researchers.


In the fields of medicine, pharmacy, and biology, in vitro is mainly used for experiments using cells.


There are many studies that look into the culturing of cells on culture plates, that observe cells, test drugs, introduce genes, and analyze cell changes. In any case, the leading role of these studies is often the ‘cell’.



In ‘in vivo’ animals are the protagonists



In vivo also has Latin origins and means ‘in a living organism’. It is often called ‘Vivo’ by Japanese researchers.

In ‘in vivo’ experiments, the protagonists are animals. Experiments using in vivo have been carried out on animals such as zebrafish, mice, rats, dogs, rabbits, pigs, monkeys, etc.

Specifically, these experiments take place to prove phenomenon that can be observed in experiments that only involve cells


It also can be considered a condition that is not artificially controlled.





What is ‘ex-vivo’? The main role is ‘organs and tissues’



Ex vivo is a Latin term which means ‘out of the living’. It is used to describe experiments in which organs and tissues are taken out of the body. This helps us research individual organs.

The experiments done via the cell (in vitro) can be reproduced in an animal (in vivo), and on many occasions, in the cell experiment, the result is different to that of an experiment that is done on an animal. Even though the experiment on the animal is often done to support the result of the original experiment, we can say that ‘this phenomenon happens in the living body, after all.


When there is a difference in results between the two experiments, it is often difficult to determine the definitive research results (although there is no doubt that this is a research result in itself). In such a case, we believe that ex-vivo research can evaluate an individual organ and could help us find the cause.

Click here for an example of an ex-vivo experiment.


Related article: [Ex-vivo organ perfusion] Application example of rat skeletal muscle to research


Related article: [Ex-vivo organ perfusion] Application example to gastrointestinal research (rat small intestine perfusion example)




A brief history of ‘in vitro’, ‘in vivo’, and ‘ex vivo’



The oldest paper in which ‘in vitro’ was described was published in 1899, (“TOXINS AND ANTITOXINS.” JAMA XXXII, no. 3 (1899): 136. https://doi.org/10.1001/jama.1899.02450300038008).


It seems that the concept of ‘in vitro’ has existed for over a century.


The oldest literature referencing ‘in vivo’’, on the other hand, is a paper on blood clotting published in 1894, (Wright, A E. "On the Influence of Carbonic Acid and Oxygen the Coagulability of the Blood in Vivo." Proceedings of the Royal Society of London 55, no. 331–335 (1894): 279–94). This document pre-dates the ‘in vitro’ paper by five years.


‘Ex-vivo’, however, is a relatively new field, compared to older ones of ‘in vivo’ and ‘in vitro. It was featured in a paper regarding the circumventing of liver in pigs in 1964, (LIEM, D. S., WALTUCH, T. L., & EISEMAN, B. (1964). FUNCTION OF THE EX-VIVO PIG LIVER PERFUSED WITH HUMAN BLOOD. Surgical forum, 15, 90–91). This was sixty-five years after the first literature of ‘in vitro’ appeared and 70 years after the first paper on ‘in vivo’.


As of June 11, 2020, Pubmed (https://pubmed.ncbi.nlm.nih.gov/) produced 1,509,490 results when searching for ‘in vitro’, and 903,143 results for ‘in vivo’: the number of papers tended to be more focused towards ‘in vitro’ studies.

To paint a clearer picture, it is easy to start experiments that are completed only by cells, and there are likely to be a number of analysis methods used for each.

On the other hand, when I tried to add animal experiments, I got the impression that + α skills (such as breeding, dissection, and procedures), are necessary.

When searching Pubmed for ‘ex vivo’, however, only 74,049 results were listed (as of June 11, 2020).


Personally, I feel that this is still quite a high number of papers, but this number is notably smaller compared to that for ‘in vitro’ and ‘in vivo’ searches (4.9% of ‘in vitro’, 8.2% of ‘in vivo’. As an area of research, it can therefore be said that it is still early to call it a ‘general field’.



Lowering the hurdles in ‘ex-vivo’ research


With our ALL-IN-ONE bioreactors, you can test animal organs with minimal pre-examination.


With regards to rat small intestines and rat skeletal muscles, we have a lineup of dedicated tubes and containers, so you can launch an experimental system with relatively few steps.

In fact, researchers conducting animal experiments are able to perform ‘ex-vivo’ perfusion of the small intestine by themselves, following just one or two instructional lectures.


It really is that easy…



Summary


To summarize the contents, at this time:


  • ‘Ex-vivo’ is the study of ‘organs and tissues’ that play a leading role outside the body

  • ‘In vitro’ is performed in a test tube, and the leading role is the study of cells

  • ‘In vivo’ is performed in the organism, leading the research in animals

  • ‘Ex-vivo’ study is not yet common and there are hurdles to getting started

We hope this has helped you gain an understanding of ‘ex vivo’, ‘in vitro’, ‘in vivo’.


Thank you for reading to the end.

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In addition to organ perfusion and ‘ex vivo’ research, we are happy to accept requests from people who want to do such perfusion, themselves, and do not yet have the know-how (we can provide the necessary advice and guidance).


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