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Simple terminology question:

  • Is there a hard boundary between in vitro and ex vivo?
  • Is there a hard boundary between in vivo and ex vivo?

Suppose a sensory neuron is electrically recorded in the following settings:

  1. Surgically accessing through the animal's skin, and patch-clamped,
  2. Tissue surrounding the neuron is almost separated, but still dangling from the larger part of the animal, and patch-clamped,
  3. Same as above, but the slight dangling connection is cut,
  4. The sensory neuron is isolated and put in an artificially oxygenated medium

The sensory neuron is assumed to have purely feedforward signal, and is perfectly healthy in all conditions. Which conditions, if any, are in vivo, in vitro, or ex vivo? (Feel free to propose better hypothetical experiments. I know this example is not the best.)

Am I the only one confused about these terminologies?

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    $\begingroup$ It's simpler and broader than that. All depends on the source material for the experiment, if you're talking about experiments: in vivo: animal models ex vivo: cultured cells in vitro: purified molecules $\endgroup$ – kjf Mar 18 '19 at 19:30
  • $\begingroup$ The terminologies are there to be helpful shorthands, i.e. they are not mutually exclusive terms and are not strictly defined jargon. Case 1 is in vivo, the rest are not. Concerning Case 2, removing the environment of a neuron cannot guarantee its native state as it exists in the organism, so it is not an in vivo experiment (at least not to most electrophysiologists). In vitro is just a shorthand for where it's taking place. You can simulate an observation on a computer in silico, or make observations on a plate in vitro. If you can't be clear with a shorthand, don't use it! $\endgroup$ – S Pr Mar 19 '19 at 13:47
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Ex vivo simply means "outside the normal, living organism", whereas in vitro means "within glass", usually in a cultured system. They are not exactly same as there is no need for the work to be done in a culture system, although both are not in vivo. Harvested tissue could be examined ex vivo without being in a test tube, or surgical systems could be tested ex vivo on artificial organ models. In vivo requires the natural, living organism, although it depends on just how much you are perturbing the natural.

To answer your scenarios,

  1. in vivo
  2. ex vivo, as it is not within the normal organism, although I could understand someone taking issue with that; definitely not in vivo, which is usually for normal conditions only, even including temperature.
  3. ex vivo
  4. If you mean the artificially oxygenated environment of a tissue culture system, then in vitro; if you mean the artificially oxygenated environment of a lab bench with an open $O_2$ valve, then ex vivo would suffice.
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  • $\begingroup$ Comment to top answer (from Amory): in vivo is not for normal conditions only, half of the times it's not in the "normal" "natural" conditions, that's how you can learn something, you always have to compare a mutated version or diseased version to a healthy control, all is in vivo anyway (when it's in vivo), regardless of the conditions. So in the example 1, are you trying to say that if it is the mouse model for Alzheimer disease, for example, then it's not in vivo anymore?! Also, "vivo" doesn't mean "living organism", it just means "living". $\endgroup$ – kjf Mar 21 '19 at 14:57
  • $\begingroup$ @kjf That was intended to convey the typical case of a living organism. Cell culture is living and is an organism, but it is not a "normal organism." It was intended to be colloquial, as noted where I say "although it depends on just how much you are perturbing the natural." $\endgroup$ – Amory Mar 21 '19 at 19:28
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(Not only) Wikipedia states that in vitro and in vivo have a very hard boundary between them. I something is studied in the context of an organism, without being extracted, it is in vivo, as soon as it is extracted it is in vitro.

Strictly speaking, I would count only the first of your neuron examples as in vivo, because it is still expected to be working like it does inside the organism. As soon as you start having it dangling out, the original "environment" is destroyed.

The relation between ex vivo and in vitro is less defined. I would count example 2 as ex vivo, but not in vitro, as the Wikipedia article for ex vivo describes. Same goes for example 3.

Example 4 is of course in vitro. Debatable is, if in vitro excludes ex vivo. It is still taken out of an organism, not grown artificially, so I would still consider it ex vivo.

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if you check articles in different fields, chemists and biochemists will usually say cultured cells is in vivo ("the molecules we always study in the tube are now inside a living cell!"), clinical doctors will say it's in vitro ("we take some cells from the patient and put them in a tube"), cell biologists working with clinical samples, animal models, cell cultures, purified molecules, the whole set, will say it's ex vivo ("the molecules that we study are in a living cell, but that living cell that we also study is out of the organism, ex vivo!").

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    $\begingroup$ Can you add some reliable references please? $\endgroup$ – L.B. Mar 21 '19 at 16:52
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The term in vivo refers to a medical test, experiment or procedure that is done on (or in) a living organism, such as a laboratory animal or human.

The term in vitro, in contrast to in vivo, refers to a medical study or experiment which is done in the laboratory within the confines of a test tube or laboratory dish.

In contrast to in vitro studies, in vivo studies are needed to see how the body as a whole will respond to a particular substance. In some cases in vitro studies of a drug will be promising, but subsequent in vivo studies fail to show any efficacy (or, on the other hand, find a drug to be unsafe) when used within the multiple metabolic processes that are continually taking place in the body.

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  • $\begingroup$ Please provide a citation or link to supporting evidence. Thanks! $\endgroup$ – theforestecologist Mar 21 '19 at 18:52

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