Resources - RESEARCH LITERACY
What does ex vivo mean? Ex vivo vs in vitro and in vivo
Ex vivo means studying living tissue or an organ after it has been taken out of the body. It sits between in vitro cell work and in vivo work in a living body.
Ex vivo means working with living tissue or a whole organ after it has been taken out of a body, while it is still functioning. The Latin means "out of the living". It sits between in vitro work, which uses cells or molecules in a dish, and in vivo work, which happens inside a whole living organism.
That middle position is the point of it. An ex vivo heart, lung or tumour sample keeps much of its real structure: the mix of cell types, the blood vessels, the way cells sit against each other. But it is cut off from the rest of the body, so the researcher can control what goes in and measure what comes out. Our companion guide, "In vitro vs in vivo", explains why results from cells in a dish so often fail in whole organisms. Ex vivo methods are one way researchers try to narrow that gap.
What is the difference between ex vivo, in vitro and in vivo?
- In vitro: cells, enzymes or microbes studied in a dish or tube, often a cell line that has been grown in the lab for many years. The most control, the least realism.
- Ex vivo: fresh tissue or a whole organ taken from a body and kept working outside it. Real tissue structure, but no circulation from the rest of the body, no liver breaking drugs down and no wider immune response.
- In vivo: the experiment happens inside a living animal or person. The most realism, the least control.
A simple rule of thumb: if the material came out of a body recently and still behaves like that tissue, it is probably ex vivo. If it is a cell line kept growing in culture, it is in vitro. If the body is still attached, it is in vivo. Labels are shorthand, so when it matters, read the methods section of a paper to see exactly what material was used and where it came from.
What is a classic example of an ex vivo experiment?
One of the oldest ex vivo methods is still in daily use. In 1895 Oscar Langendorff pioneered the isolated perfused mammalian heart. The heart is removed and kept beating by pumping a nutrient fluid through it in reverse, which is why it is called retrograde perfusion.
A 2011 review in the Journal of Molecular and Cellular Cardiology by Bell, Mocanu and Yellon describes how this preparation has supported research on how the heart contracts, how blood flow through the heart's own arteries is controlled, and how heart muscle uses energy. It is also used as an ex vivo model of the damage that happens when blood flow to the heart is cut off and then restored.
The appeal is control. A researcher can change one thing, such as a drug or a period of low flow, and measure the heart's response directly, without nerves, hormones or other organs getting in the way. That is also the weakness. In a living body, those other influences are part of what decides the outcome.
Can ex vivo tests on a patient's own cells guide treatment?
A newer use is testing drugs on a patient's own cancer cells, taken fresh from a biopsy. In a 2017 pilot study in The Lancet Haematology, Snijder and colleagues used automated microscopy to measure how single cells in biopsy samples from people with aggressive blood cancers responded to a panel of drugs. They called the approach pharmacoscopy.
Looking back at 20 people with newly diagnosed acute myeloid leukaemia, the test predicted their response to first treatment with 88.1% accuracy. In the forward-looking part of the study, 17 patients received treatment chosen with the test's help. Of these, 15 (88%) responded, compared with 4 of 17 (24%) on their previous treatment. The authors described this as an interim analysis of a small, single-arm study that warranted further investigation. That is the right reading: promising ex vivo results still need properly controlled trials in people.
How is ex vivo perfusion used in organ transplants?
Ex vivo methods have also moved from the lab into hospitals. The standard approach is to store donor organs cold. With warm, or normothermic, perfusion the organ is kept at body temperature and supplied with fluid outside the body, so its function can be checked before it is transplanted.
In a 2011 study in the New England Journal of Medicine, Cypel and colleagues placed 23 high-risk donor lungs on an ex vivo circuit for four hours. Twenty stayed stable and were transplanted. Serious early graft problems at 72 hours occurred in 15% of these, compared with 30% of 116 lungs transplanted the usual way, a difference that was not statistically significant. The authors concluded the results were similar to those with conventionally selected lungs. It was not a randomised trial.
A randomised trial came later for livers. In 2018, Nasralla and colleagues reported in Nature on 220 liver transplants comparing warm machine perfusion with cold storage. Warm preservation was linked to a 50% lower level of graft injury, measured by liver enzymes, a 50% lower rate of discarded organs and a 54% longer average preservation time. There was no significant difference in bile duct complications, graft survival or patient survival.
What is ex vivo gene therapy?
In medicine, ex vivo also describes treatments where cells are taken out, changed in a laboratory and returned. In November 2023 the MHRA authorised Casgevy for sickle cell disease and transfusion-dependent beta-thalassaemia in patients aged 12 and over. The MHRA described it as the first licensed medicine to use the CRISPR gene-editing tool. Stem cells are taken out of the bone marrow, edited in a laboratory and then infused back into the patient.
Early human evidence came from a 2021 report in the New England Journal of Medicine by Frangoul and colleagues, describing the first two patients to receive their own stem cells after CRISPR editing outside the body. This is a different use of the term from the lab models above, but the idea is the same: the work on the tissue happens out of the body.
What are the limits of ex vivo research?
- Time. Tissue can only be kept working outside the body for a limited period. The lung study above used four hours of perfusion.
- No whole-body context. There is no liver to break a drug down, no kidneys to clear it, and usually no wider immune system. A drug that works on an isolated tumour sample still has to reach that tumour inside a person.
- Small numbers. Fresh human tissue is hard to obtain, so many ex vivo studies are small, like the 17-patient group in the pharmacoscopy study.
So where does ex vivo evidence sit? Above a cell line in a dish for realism, and below a well-run trial in people for answering whether something actually helps. When you see ex vivo in a headline, ask the same question you would ask of in vitro work: has this been tested in living people, in a controlled trial?
This article is for general education about research methods. It is not medical advice, and it does not suggest that any treatment mentioned is suitable for any individual.
Frequently asked
- What does ex vivo mean?
- Ex vivo means working with living tissue or a whole organ after it has been taken out of a body, while it still functions. The Latin means "out of the living". It keeps much of the tissue's real structure, but it is cut off from the rest of the body, so researchers can control what goes in and measure what comes out.
- Is ex vivo the same as in vitro?
- Not quite. In vitro usually means cells or molecules in a dish, often a cell line grown in the lab. Ex vivo means fresh tissue or a whole organ taken from a body and kept working outside it. Ex vivo keeps more of the real tissue structure, but neither has the whole body around it, which only in vivo studies provide.
- What is an example of ex vivo research?
- A classic example is the isolated beating heart, a method Oscar Langendorff pioneered in 1895 and still used today. Newer examples include testing cancer drugs on a patient's own biopsy cells, and keeping donor lungs or livers warm and perfused outside the body so their function can be checked before transplant.
- What is ex vivo gene therapy?
- It is a treatment where a patient's own cells are taken out, changed in a laboratory and given back. Casgevy, authorised by the MHRA in November 2023, works this way: stem cells are taken from the bone marrow, edited using CRISPR in a laboratory, then infused back into the patient.
The studies and sources behind this page
- Bell RM, Mocanu MM, Yellon DM. Retrograde heart perfusion: the Langendorff technique of isolated heart perfusion. J Mol Cell Cardiol 2011;50:940-950.
- Snijder B, Vladimer GI, Krall N et al. Image-based ex-vivo drug screening for patients with aggressive haematological malignancies: interim results from a single-arm, open-label, pilot study. Lancet Haematol 2017;4:e595-e606.
- Cypel M, Yeung JC, Liu M et al. Normothermic ex vivo lung perfusion in clinical lung transplantation. N Engl J Med 2011;364:1431-1440.
- Nasralla D, Coussios CC, Mergental H et al. A randomized trial of normothermic preservation in liver transplantation. Nature 2018;557:50-56.
- Frangoul H, Altshuler D, Cappellini MD et al. CRISPR-Cas9 gene editing for sickle cell disease and beta-thalassemia. N Engl J Med 2021;384:252-260.
- Medicines and Healthcare products Regulatory Agency. MHRA authorises world-first gene therapy that aims to cure sickle-cell disease and transfusion-dependent beta-thalassemia. GOV.UK, 16 November 2023.
Lessons on this topic
Related reading
Educational content only. Not medical advice, diagnosis or treatment. Always consult a qualified healthcare professional before changing your health regimen.