Ex vivo

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Figure 1: Ex vivo brainstem: (A) coronal view displaying the anterior portion of the tissue sample, (B) sagittal view displaying the left-hand side of the tissue sample[1]

Ex vivo (Latin: "out of the living") literally means that which takes place outside an organism.[2] In science, ex vivo refers to experimentation or measurements done in or on tissue from an organism in an external environment with minimal alteration of natural conditions.[2] Testing the effect of compounds on skin biopsies is an example of ex vivo research, while isolating the primary cells from that biopsy and creating a 3D cell culture model is an example of in vitro research.[3] Both use human tissues, but the former is a more complex and translational environment for drug testing.

A primary advantage of using ex vivo tissues is the ability to perform tests or measurements that would otherwise not be possible or ethical in living subjects. Tissues may be experimented on in many ways, including in part (e.g. cardiac contractility models using atrial pectinate muscles) or as whole organs (e.g. isolated perfused heart model).

Examples of ex vivo models include:

  • Cardiovascular safety models using cardiac tissues or blood vessels[4]
  • Inflammatory studies using skin biopsies[5]
    A plat containing a square sample of human skin with circular biopsies removed from it
    Figure 2: Human skin tissue: Human skin tissue with full-thickness punch biopsies removed for use in an ex vivo culture model
    (see figure 2)
  • Isolated perfused heart models[6]
  • ADME/DPMK studies using the Ussing Chamber system[7]

Application of ex vivo models in drug discovery[edit]

Demonstration of isolation of choroid from the mouse eye

In drug discovery, ex vivo procedures use living tissues taken from an organism and cultured in a laboratory apparatus under sterile conditions. There are several specialized platform technologies designed for ex vivo pharmacological research, including Ussing chambers, organ baths and wire myographs. Experiments begin as soon as possible after tissue procurement to maintain the physiological function and viability of the samples.[8]

Differences between ex vivo VS in vitro models[edit]

There are distinct differences between ex vivo and in vitro models that make them more suitable for certain applications and drug development stages than others. In general, in vitro models are used at an earlier stage in development as they are higher throughput than ex vivo models. Examples of drug discovery phases where in vitro models are commonly used include target identification, validation, and lead validation.[9]

Conversely, ex vivo models are used when a test article is closer to clinical trials to validate preclinical data in a functioning human system e.g. lead optimization and pre-clinical safety.[9] Ex vivo models can also be used after a drug reaches clinical trial to investigate issues that were not identified using in vivo or in vitro studies.[10] The main features of each approach and how they differ is summarized in the table below (table 1).

Feature Ex vivo In vitro
Translatability High clinical translatability Low clinical translatability
Applicable to clinical trouble-shooting Yes - can be used to troubleshoot clinical issues Can be used but lack clinical translatability
Throughput Low throughput High Throughput
Ethical considerations Many ethical considerations when workjing with human tissues and organs Less ethical consideration
Cost Expensive to obtain samples Relatively inexpensive
Sample procurement Can be difficult to obtain fresh tissue samples Easy to obtain primary cells commercially
Level of expertise Require specialised lab equipment and knowledge Equipment and protocols more easily obtained
Accounts for inter-individual differences Yes as donor tissue used Yes but only if primary cell lines are used

Table 1: Exploring the differences between ex vivo and in vitro models for drug development.

In situ lung function evaluation, and assessment of total lung capacity (TLC) and basal elastance after performing a recruitment maneuver

See also[edit]

References[edit]

  1. ^ 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.
  2. ^ a b Gowing, Genevieve; Svendsen, Soshana; Svendsen, Clive N. (2017). "Ex vivo gene therapy for the treatment of neurological disorders". Functional Neural Transplantation IV - Translation to Clinical Application, Part A. Progress in Brain Research. Vol. 230. pp. 99–132. doi:10.1016/bs.pbr.2016.11.003. ISBN 9780128117385. PMID 28552237.
  3. ^ Puckrin, Zara (29 March 2022). "Skin biopsy and ex vivo culture methods" (Blog). reprocell.com. REPROCELL. Retrieved 4 April 2022.
  4. ^ Puckrin, Zara. "Cardiovascular safety pharmacology studies in human fresh tissues". www.reprocell.com. Retrieved 2022-08-05.
  5. ^ Puckrin, Zara. "Skin biopsy and ex vivo culture methods". www.reprocell.com. Retrieved 2022-08-05.
  6. ^ Puckrin, Zara (24 May 2022). "Limitations of the isolated perfused heart and alternative models". www.reprocell.com. Retrieved 2022-08-05.{{cite web}}: CS1 maint: url-status (link)
  7. ^ Puckrin, Zara. "How to estimate drug permeability using the Ussing Chamber technique". www.reprocell.com. Retrieved 2022-08-05.
  8. ^ Linder, Roland (14 March 2022). "What is Human Tissue Testing?". www.reprocell.com. Retrieved 2022-08-05.{{cite web}}: CS1 maint: url-status (link)
  9. ^ a b "Drug Discovery Phases". www.reprocell.com. Retrieved 2022-08-05.
  10. ^ Amouzadeh, Hamid R.; Dimery, Isaiah; Werner, Jonathan; Ngarmchamnanrith, Gataree; Engwall, Michael J; Vargas, Hugo M.; Arrindell, Deborah (2019-10-01). "Clinical Implications and Translation of an Off-Target Pharmacology Profiling Hit: Adenosine Uptake Inhibition In Vitro". Translational Oncology. 12 (10): 1296–1304. doi:10.1016/j.tranon.2019.05.018. ISSN 1936-5233.