Hi Lucie,

I had similar findings when i was finishing up my PhD, and funnily enough a reviewer asked me to correct my terminology of in vitro to ex vivo as I was culturing primary Drosophila haemocytes, not in vitro cell lines like Drosophila S2 cells. So as an answer to your question, specifically toward cells and cell culturing, if you were dealing with 'immortalised' cell lines like Drosophila S2 cells, HeLa cells...any other cultured cell line, these are termed as in vitro, obviously referring to the latin 'within glass' (as most have stated above). Whereas cells within an organism are clearly in vivo referring to the latin 'within living', but when you remove/ isolate/ extract these in vivo cells from the organism and place into a culture condition you are now dealing with ex vivo. So from what I know and have experienced so far, there is somewhat of a method to divide these terms/ conditions, whereby you not only consider the cell itself but also the conditions. The cells are obviously living (therefore you would think in vivo), but they are cultured (therefore you would think in vitro)...naturally self conflicting already! But once you consider the culture conditions i.e. the surrounding environment the cells (primary cells in my case) are cultured within, you can now make a division. In my opinion, in vitro cells are immortalised cell lines that are able to survive in relatively harsh conditions (some cell lines are more robust than others). In vivo cells are not necessarily immortalised as there is a particular fate mapped out and obviously reside within the optimum conditions of the host organism. And lastly ex vivo cells are not necessarily immortalised but now cultured outside the host organism but kept in a culture environment that is close to the optimum conditions of the host i.e. on a 2D or 3D extracellular matrix, culture media that is relative to the organism, and any other crazy cooky conditions that are figured out to optimise for that particular cell type. Anyways I hope this has helped out a little, and it would be interesting to see more of what people think.

Best,

Chris

I think in vitro means that like for example in a PCR experiment you put each component of a thing happening in a cell together without having a cell... A cell culture is doing its things on its own.. You "just" provide the habitat..

I think cell culture experiments are considered as in vitro studies rather than in vivo, so I agreed with u.

When thinking about natural science involving multi-cellular organisms.

In vivo is in the body. The term "In vivo" used for experiments done in cell cultures is poor language and these people need to hire language help before they publish. The term for experiments done on cells in culture can be in vitro. Ex vivo can also be used and applies for cells cultured after (recent) from removal from the body.

Unfortunately, there is no good latin term for experiments done on cells in general. Relative to biochemical/molecular studies done on components outside the cell.

Terms like in cellulo have been suggested but I still find them clumsy.

You are right that cells in culture are not an organism. However, personally I do think they are living, albiet with assistance from a human or machine.

Check the requirments (always changing) for qualifying as living here. :-)

http://en.wikipedia.org/wiki/Life

@Norbert, not exactly. In your terms, a molecule like DNA polymerase (extracted from a cell just like cells in culture are extracted from an organsim) also acts on its own and you "just" provide the conditions (of the molecule's habitat). Actually, "in vivo" means "in living organism", not "in living cell". In cell culture you put components of a thing happening in organism (cells, hormones, cytokines, growth factors, nutrients etc) together without having an organism.

"In vivo" is a complete living organism with her/his systems.

http://en.wikipedia.org/wiki/In_vivo

A bactery is complete, an human cell not.

In vivo experiment is within living organism so the cell culture should be considered as in vitro and not in vivo.

In dear old times, there was a strict consensus of the usage of in vivo, but there was a debate should in vitro be applied to continuous cell line only or be inclusive for primary cell culture. This condradiction, however, didn't expand in vivo to primary cultures. It was adopted by the majority and is reflected in specific literature that cells derived from an organism grow (or are just maintained) in vitro. This is reflected in the scope of In vitro journals (see, for example, http://www.sivb.org/pubs_a_index.asp and http://www.sivb.org/pubs_p_index.asp). The usage of in vivo for a cell culture is odd, that's what I say.

Thank you all for your answers.

Agreeing with most of you, even I feel better using (and reading) "in vitro" for the cell culture experiments. However, I still feel a big difference between PCR and cell-based experiments. What is the problem with using another term for that?

@ Steven: why do you find the term "in cellulo" clumsy? Is it because its inacurracy or for some other reason? With my very basic latin, i see even "in silico" as a little inexact term but totally clear when widely used.

@ Lucie

To clarify, my previous comments were from a molecular immunologists viewpoint where primary and cell line cultures are my bread and butter.

in cellulo simply "feels" clumsy to me. It's a personal thing. Maybe because I never learned this as a term in school. Or because it does not feel as proper latin as in vitro or in vivo. I'm sure you could use the term and people would understand what you mean though. Sometimes it's better to find a work-a-round than to use a somewhat ambiguous term when writing.

In silico is known as a proper term for within silicon. Generally referred to by biologists performing controlled experiments with computers. So it feels proper to me.

Proper science writing is quite difficult when finding that balance of accuracy, no over interpretation, but still with room for reasonable speculation. And once you find it the reviewers demand you turn it into their paper instead. :-p

That depends on what experiments the papers are talking about. Eg. for protein-protein interaction analysis, some people consider the Co-IP in the cell culture "in vivo" (the protein-protein interaction occurs inside the living cells); whereas two purified proteins' binding in eppendorf tube is sometimes considered "in vitro" (the protein-protein binding occurs outside the living body and which is the cell).

As you have noted it correctly, it should have been "in-vitro" or "ex-vivo"....The editor of the respective journal should have noted this!!

In-vivo is "within organism" and the cultured cell is not an "organism"

Sorry Hong but this is wrong: "some people consider the Co-IP in the cell culture "in vivo". People don't get to decide the definition of a word as they want them to be... "in vivo" and "in vitro" have clear definition...

Ex vivo sounds more apt....specially when you are working with primary cell culture....else cell lines are essentially in vitro, though, technically they are ex vivo too....

Hi Lucie,

I had similar findings when i was finishing up my PhD, and funnily enough a reviewer asked me to correct my terminology of in vitro to ex vivo as I was culturing primary Drosophila haemocytes, not in vitro cell lines like Drosophila S2 cells. So as an answer to your question, specifically toward cells and cell culturing, if you were dealing with 'immortalised' cell lines like Drosophila S2 cells, HeLa cells...any other cultured cell line, these are termed as in vitro, obviously referring to the latin 'within glass' (as most have stated above). Whereas cells within an organism are clearly in vivo referring to the latin 'within living', but when you remove/ isolate/ extract these in vivo cells from the organism and place into a culture condition you are now dealing with ex vivo. So from what I know and have experienced so far, there is somewhat of a method to divide these terms/ conditions, whereby you not only consider the cell itself but also the conditions. The cells are obviously living (therefore you would think in vivo), but they are cultured (therefore you would think in vitro)...naturally self conflicting already! But once you consider the culture conditions i.e. the surrounding environment the cells (primary cells in my case) are cultured within, you can now make a division. In my opinion, in vitro cells are immortalised cell lines that are able to survive in relatively harsh conditions (some cell lines are more robust than others). In vivo cells are not necessarily immortalised as there is a particular fate mapped out and obviously reside within the optimum conditions of the host organism. And lastly ex vivo cells are not necessarily immortalised but now cultured outside the host organism but kept in a culture environment that is close to the optimum conditions of the host i.e. on a 2D or 3D extracellular matrix, culture media that is relative to the organism, and any other crazy cooky conditions that are figured out to optimise for that particular cell type. Anyways I hope this has helped out a little, and it would be interesting to see more of what people think.

Best,

Chris

"In vivo" definitely means within a living being, living, alive body ! Cell culture lines can be termed as "ex vivo" more appropriately !

Why not call it "in vitro cell culture" to distinguish from other "in vitro" methods? The term "ex-vivo" is typically understood among the medical and veteninarian research community as perfomring an experiment outside the body on an intact organ, tissue, or extracted cells from peripheral blood, bone marrow, or lymphatics. The term "ex-vivo" is not associated with cell culture experiments among the medical research community.

Yes you are right in vivo actually means an experiment being done in the live animal. In fact even ex vivo terminology would be wrong. Ex vivo is normally used to when cells like bone marrow cells are harvested from the animals and then cultured for assesment of various parameters.

My understanding is, there is significant overlap between in vitro and ex vivo. However, some sources define ex vivo as something done to cells removed from the living organism, whereby the cells are then returned to the living organism, as in dendritic cell vaccination (where the cells are removed from the body, stimulated in the lab, and injected back into patients). If the cells are not returned thereafter to the living organism, then it's just plain in vitro. In my discipline, biological membranes are removed from animals for pharmaceutical studies. In some cases we don't care if the membranes remain biologically viable, and we just refer to them as in vitro experiments. If biological viability is key, then we call them ex vivo experiments. But to be honest, every other person probably has his/her own view on this that differs from mine.

I would agree though that cell culture experiments are not in vivo. To me, the term "in vivo" implies the presence of systemic function, a system being made up of multiple organs, which cannot exist in cell cultures (even co-cultures or organotypic cultures). I personally would never refer to cell cultures as in vivo.

In our lab we use the term ex vivo in reference to experiments done using cells that have been freshly isolated from a living organism. I would agree that use of the term in vivo should be reserved for phenomena that occur within an intact organism.

in vivo is means you can do your experiment inside a live animal and or human or lab animals

In vivo means you do experiment wihtin live organism.

And "in situ" in biological or medical experiments usually means "in position or location." As when one examines the effects of a drug not on isolated particular biomolecules but in a whole organ, as a perfused lung. See http://en.wikipedia.org/wiki/In_situ#Biology_and_Biomedical_Engineering

I agree with Ritu Trivedi In vivo is an experiment within the live animal. Cell culture experiments are not in vivo experiments. lalitha kabilan

I agree with James Bowman. Whether it is a primary or secondary culture of cells or a long term culture of cell line, it is "in vitro cell culture or in vitro cell line culture or in vitro culture of cell line" and if cells are being studied inside the body, it is "in vivo" studies or observations.

I really fail to understand the unnecessary confusion in this discussion here. Cells, anyways, are not created very often or commonly inside glass or in culture. The cells are to be isolated out a living body or organ, and then cultured "in vitro or inside glass" Of course, few labs are engaged in creation of cells from various molecules.

Hence, either the cells are inside the living body i.e. in vivo, or outside the living body inside the cell culture i.e. in vitro. The term ex vivo is used for entirely different purpose, and if being used for cell culture, it should be critically reviewed, as the term "ex-vivo" is not associated with cell culture experiments, I suppose, in any research community, even not among veterinary research community as well.

Here, I agree with Steven Applequist that before publication of such erroneous terms, they should be corrected in proper perspectives by hiring language helpers, instead of spreading the unnecessary confusion among researchers.

And why not simply: in vivo, what happens in the body, in vitro wat happens in an artificially reconstitued environment.

I say "in vitro" in your case

I agee with Nichole. However, I understand ex vivo as a type of in vitro experiment where biological viability is key difference.

'in vivo' means anything done inside a living body and 'in vitro' means not in the body. Tuberculin test is though done on the skin is a 'in vivo' test. Any test done on bacterial cell or fungal cell in a culture media is a in vitro test, though bacteria or fungus are living cell.Quantiferon TB assay is done with living lymphocyte culture, is a 'in vitro' test. Ex vivo meaning experiment done in cell culture i,e cells outside the body. Actually it should be called as a 'in vitro' test.

A slight detour on this question, if I may? I am reviewing a student paper in which the term "in vivo" is used to describe qualitative research (e.g., that categories or themes emerge "using primarily in vivo language."

What's your take on that? Incorrect use of the term? Or acceptable?

On odd turn of phrase but, in appropriate context, I can see using the term "in vivo language" to refer to how research is described, communicated, and reported.

Thanks, James

We use "in vivo" with all the body systems, in the whole living creature. If it is only a cell like a bacterium or yeast, one cell is complete. But in pluricellular not, must be complete  body and alive moment.

For example, if you study a drug, many times is different the effect in a cell culture than in the whole living creature, because all the systems are connected, and it can be good at cell level but toxic in the whole body.

In pharmaceutical research if we said "in vivo" we talk about all the body with all the physiological systems (normally).

You are right experiments done inside the body of animals are to be considered as in vivo. However, sometimes we dislodge cells from the body parts like bone marrow cells after the treatment to the animals. So these are cells that have been extracted from the tissues. But we call them ex vivo rather than in vivo.

In general I agree with James Bowman, but not certain that I would use the term in vitro cell culture. My working definitions are as follows: 1) In vivo - in living organism (e.g., human, mouse, squid, volvox, E-coli); 2) Ex vivo - outside of living organism (e.g., cells on excised tissue, hematopoietic cells, organ culture*); 3) In vitro - outside of living organism and outside of cells (e.g., in vitro transcription). *Organ culture is a special case, one could have de novo organ culture, which in itself is a fascinating field, and you can have ex vivo organ culture (i.e., organ excised from living organims and maintained in culture).

Cell culture for me doesn't strictly fall within any of these definitions and is dependent on the context. Culturing hematopoietic cells outside the body is strictly "ex vivo culture", while culturing epithelial/fibroblast cells that must first be isolated from ex vivo tissue I prefer to call primary cell culture. The use of in vitro for cell culture I don't think  does it justice.

Similarly, folks use the term ex vivo expansion for both hematopoietic and epithelial cells, the former being far more common in the literature. This just confuses the issue and I would argue that it is best to restrict ex vivo expansion to hematopoietic cells and primary cell expansion to non-hematopoietic cells (epithelial and mesenchymal cells).

In the end, this is an issue of nomenclature and I think it's about time to develop a proper nomenclature to avoid confusion especially in instances where translational research is involved.

I think it depends on the context!

I am studying pre-mRNA alternative splicing of several genes. It is possible to collect the  nuclear extract from a given cell line and perform the splicing reaction in plastic tubes. This should be termed 'in vitro' without a doubt.

But when I analyze splicing in a living cell, endogenous/minigene transfected, it is difficult to use the term 'in vitro'. If you give me a choice between 'in vitro' & 'in vivo', I'd pick 'in vivo' in this scenario. 

I agree with most of what has already been said, just wanted to add that one can always say "in cells" rather than "in vitro/in vivo" to be precise. A cell biologist will usually consider cultured cells "in vivo" and a system reconstituted from e.g. cell extract or purified components "in vitro". If cultured cells would be "in vitro" it would leave no term for the numerous cell-free "in vitro" assays that researchers have developed and continue to develop and that are instrumental for obtaining molecular level insight into cellular processes.