Ex vivo

Ex vivo (Latin for 'out of the living') refers to experiments or measurements performed on tissues or cells that have been removed from an organism and maintained under conditions that closely mimic their natural environment. While certain ex vivo techniques have been employed since the early 20th century, their formalization and refinement as a research methodology accelerated in the mid-20th century. These approaches enable the study of biological processes in a controlled setting while preserving the structural and functional integrity of tissues and organs. Ex vivo studies are widely applied in medical research, pharmacology, and biotechnology, serving as an intermediate method between in vitro (test tube) experiments and in vivo (whole-organism) studies. They provide a balance between experimental control and physiological relevance, allowing for investigations that may be ethically or technically impractical in living subjects.[2][3][4]
Techniques
[edit]Ex vivo research uses specialized techniques to sustain tissues or cells outside their natural environment while preserving their functional integrity. In ex vivo organ perfusion, whole organs—such as the heart or lungs—are maintained in a functional state by circulating solutions that mimic physiological blood flow. This method enables researchers to investigate organ-level responses to drugs, disease states, or environmental changes under controlled conditions. In contrast, traditional organ culture typically involves maintaining organ sections or small fragments in static or semi-static conditions without active perfusion.[7][8]
Another widely used technique is organotypic slice cultures, where thin sections of organs, such as the brain or liver, are maintained on supportive matrices to preserve their three-dimensional structure and cellular interactions. This method enables the study of localized responses, tissue-specific dynamics, and physiological processes over extended periods.[9][10][11] An example is the use of hippocampal slices in neuroscience research to examine long-term cellular and synaptic activity.[12] In some cases, ex vivo electroporation, in which an electric field is applied to cells to facilitate the uptake of genetic material, is used to introduce DNA into cells within tissue slices, allowing researchers to study gene expression in a controlled environment.[13]: 241
Cell culture involves isolating individual cells from tissues and growing them in a medium enriched with nutrients and growth factors. While these cultures retain some functional characteristics of their tissue of origin, they often exhibit changes in phenotype and gene expression when removed from their native environment. Primary cell cultures, derived directly from tissues, more closely resemble physiological conditions than immortalized cell lines, making them essential for studying cellular behavior, disease mechanisms, and drug effects.[14][15]
In electrochemistry
[edit]In electrochemical research, ex vivo methods provide a controlled platform for investigating biological analytes with a degree of experimental flexibility not achievable in in vivo studies.[16]: 161–164 The constraints of living systems limit electrode design and placement in in vivo experiments, where smaller electrodes, such as micro- and nanoelectrodes, are typically preferred to minimize invasiveness.[17]: 3–4 By contrast, ex vivo techniques allow for the development of custom electrode geometries, enabling precise interfaces with biological tissues under controlled conditions. This adaptability facilitates a detailed examination of analytes and their roles in physiological processes. Ex vivo electrochemical techniques are applied in neuroscience, pharmacology, and biomedical engineering to study neurotransmitter dynamics, metabolic activity, and disease-associated biomarkers.[16]: 161–164
See also
[edit]- Animal testing – Use of animals in experiments
- List of medical roots, suffixes and prefixes
- Neoclassical compound – Compound words composed from Latin or ancient Greek
References
[edit]- ^ Ford, Anastasia A.; Colon-Perez, Luis; Triplett, William T.; Gullett, Joseph M.; Mareci, Thomas H.; Fitzgerald, David B. (2013). "Imaging White Matter in Human Brainstem". Frontiers in Human Neuroscience. 7: 400. doi:10.3389/fnhum.2013.00400. PMC 3721683. PMID 23898254.
- ^ Makdisi, G; Makdisi, T; Jarmi, T; Caldeira, CC (2017). "Ex vivo lung perfusion review of a revolutionary technology". Annals of Translational Medicine. 5 (17): 343. doi:10.21037/atm.2017.07.17. PMC 5599284. PMID 28936437.
- ^ Griffiths, John R. (2022). "Magnetic resonance spectroscopy ex vivo: A short historical review". NMR in Biomedicine. 35 (4): e4740. doi:10.1002/nbm.4740. PMID 35415860.
- ^ Maroli, Amith Sadananda; Powers, Robert (2023). "Closing the gap between in vivo and in vitro omics: using QA/QC to strengthen ex vivo NMR metabolomics". NMR in Biomedicine. 36 (4): e4594. doi:10.1002/nbm.4594. PMC 8821733. PMID 34369014.
- ^ Shao, Zhuo; Friedlander, Mollie; Hurst, Christian G.; Cui, Zhenghao; Pei, Dorothy T.; Evans, Lucy P.; Juan, Aimee M.; Tahir, Houda; Duhamel, François; Chen, Jing; Sapieha, Przemyslaw; Chemtob, Sylvain; Joyal, Jean-Sébastien; Smith, Lois E. H. (2013). "Choroid Sprouting Assay: An Ex Vivo Model of Microvascular Angiogenesis". PLOS ONE. 8 (7): e69552. Bibcode:2013PLoSO...869552S. doi:10.1371/journal.pone.0069552. PMC 3724908. PMID 23922736. S2CID 466393.
- ^ Bassani, Giulia Alessandra; Lonati, Caterina; Brambilla, Daniela; Rapido, Francesca; Valenza, Franco; Gatti, Stefano (2016). "Ex Vivo Lung Perfusion in the Rat: Detailed Procedure and Videos". PLOS ONE. 11 (12): e0167898. Bibcode:2016PLoSO..1167898B. doi:10.1371/journal.pone.0167898. PMC 5148015. PMID 27936178.
- ^ Menander, M.; Attawar, S.; Mahesh, BN.; Tisekar, O.; Mohandas, A. (2024). "Ex vivo lung perfusion and the Organ Care System: a review". Clinical Transplant Research. 38 (1): 23–36. doi:10.4285/ctr.23.0057. PMC 11075812. PMID 38725180.
- ^ Martins, Paulo N.; Del Turco, Serena; Gilbo, Nicholas (2022). "Organ Therapeutics During Ex-Situ Dynamic Preservation: A Look Into the Future". European Journal of Transplantation. 1 (1): 63–78. doi:10.57603/EJT-010.
- ^ Peng, Michael; Margetts, Tyler J.; Sugali, Chenna Kesavulu; Rayana, Naga Pradeep; Dai, Jiannong; Sharma, Tasneem P.; Raghunathan, Vijay Krishna; Mao, Weiming (2022). "An ex vivo model of human corneal rim perfusion organ culture". Experimental Eye Research. 214: 108891. doi:10.1016/j.exer.2021.108891. PMC 8792355. PMID 34896309.
- ^ Humpel, Christian (2015). "Organotypic brain slice cultures: a review". Neuroscience. 305: 86–98. doi:10.1016/j.neuroscience.2015.07.086. PMC 4699268. PMID 26254240.
- ^ Siwczak, Fatina; Hiller, Charlotte; Pfannkuche, Helga; Schneider, Marlon R. (2023). "Culture of vibrating microtome tissue slices as a 3D model in biomedical research". Journal of Biological Engineering. 17 (1): 36. doi:10.1186/s13036-023-00357-5. PMC 10233560. PMID 37264444.
- ^ Jang, Sooah; Kim, Hyunjeong; Kim, Hye-Jin; Lee, Su Kyoung; Kim, Eun Woo; Namkoong, Kee; Kim, Eosu (2018). "Long-Term Culture of Organotypic Hippocampal Slice from Old 3xTg-AD Mouse: An ex vivo Model of Alzheimer's Disease". Psychiatry Investigation. 15 (2): 205–213. doi:10.30773/pi.2017.04.02. PMC 5900409. PMID 29475217.
- ^ Carter, Matt; Shieh, Jennifer C. (2015). "11. Gene Delivery Strategies". Guide to Research Techniques in Neuroscience (2nd ed.). Academic Press. ISBN 9780128005972 – via Google Books.
- ^ Pan, Cuiping; Kumar, Chanchal; Bohl, Sebastian; Klingmueller, Ursula; Mann, Matthias (2009). "Comparative proteomic phenotyping of cell lines and primary cells to assess preservation of cell type-specific functions". Molecular & Cellular Proteomics. 8 (3): 443–450. doi:10.1074/mcp.M800258-MCP200. PMC 2649808. PMID 18952599.
- ^ Nilsson, Linnéa M.; Castresana-Aguirre, Miguel; Scott, Lena; Brismar, Hjalmar (2020). "RNA-seq reveals altered gene expression levels in proximal tubular cell cultures compared to renal cortex but not during early glucotoxicity". Scientific Reports. 10 (1): 108891. Bibcode:2020NatSR..1010390N. doi:10.1038/s41598-020-67361-3. PMC 7316724. PMID 32587318.
- ^ a b Patel, Bhavik A. (2021). "8. Measurement from ex vivo tissues". Electrochemistry for Bioanalysis. Elsevier. ISBN 9780128215357 – via Google Books.
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