Ex vivo

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

Ex vivo (Latin for 'out of the living') refers to experiments or measurements performed on biological materials—such as tissues, organs, or cells—that have been removed from an organism and maintained under conditions that, to some extent, mimic their natural environment. This approach preserves the functional viability and structural integrity of the extracted materials for a limited time, enabling the study of biological processes in a controlled setting. 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. Ex vivo studies are widely applied in medical research, pharmacology, and biotechnology, serving as an intermediate method between in vitro and in vivo studies. They provide a balance between experimental control and physiological relevance, allowing for investigations that may be ethically or technically impractical in living subjects.

Advantages and limitations

Ex vivo, meaning 'out of the living' in Latin, refers to biological studies conducted on tissues, organs, or cells that have been removed from an organism and maintained in a controlled environment outside the body, preserving functional viability and structural integrity of the extracted materials for a limited time. As these materials are subject to degradation over time, the controlled environment typically includes oxygenation, nutrient supply, as well as regulated temperature and humidity—often facilitated through cell culture media or specialized chambers. As an intermediate approach between in vitro studies, which traditionally use isolated cells in artificial conditions, and in vivo studies, which occur within a living organism, ex vivo models offer greater organizational complexity than the former while reducing the variables inherent in the latter. Ex vivo models retain more of the tissue's natural structure than traditional cell cultures, while allowing for more controlled experiments than those conducted in living organisms. This approach may offer ethical considerations, as ex vivo models can potentially reduce reliance on animal testing for certain types of biological research.

In dermatological research, human skin organ culture (hSOC)—a technique where excised human skin is maintained in an artificial medium while preserving its natural structure—is used to investigate wound healing, drug penetration, and toxicology, leveraging the preservation of skin architecture, including appendages. These models facilitate the study of conditions unique to human skin, such as keloids, which cannot be accurately replicated in animal models. Skin explants from surgical procedures provide insights into early-stage physiological responses to laser treatments that closely resemble in vivo observations, though processes like re-epithelialization occur more slowly than in living tissue. In intervertebral disc research, ex vivo models that retain vertebral bone allow for testing potential drugs and investigating loading effects on disc degeneration and repair. In biosensing and electroanalytical applications, ex vivo methods offer experimental flexibility unavailable in living systems. While in vivo experiments typically favor smaller electrodes—micro- and nanoelectrodes—to minimize invasiveness, larger electrodes can be used in certain applications. Ex vivo approaches, by contrast, permit custom electrode geometries that interface precisely with biological tissues under controlled conditions, without the same constraints on size and invasiveness. This adaptability enables detailed examination of biological analytes and their physiological roles. Ex vivo electrochemical methods are applied in neuroscience, pharmacology, and biomedical engineering to study neurotransmitter dynamics, metabolic activity, and disease-associated biomarkers.

However, ex vivo models have inherent limitations, including significant changes in biophysical properties of tissues after the organism's death, tissue degradation that increases with time, restricted viability duration, as well as absence of whole-body physiological responses, such as lack of blood circulation and nerve innervation. These constraints prevent the models from replicating long-term or systemic effects. The comparison between in vivo and ex vivo models can be complex due to these changes in tissue properties. For instance, studies have found large changes in electric fields between in vivo and ex vivo measurements that increased with postmortem time.

Techniques

Further information: Ex vivo lung perfusion and Machine perfusion

Demonstration of isolation of choroid from the mouse eye

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

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. By contrast, organ culture traditionally involves maintaining organ sections or small fragments in static or semi-static conditions without active perfusion.

Another widely used technique is organotypic slice cultures, where thin sections of organs 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. An example is the use of hippocampal slices in neuroscience research to examine long-term cellular and synaptic activity. 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.

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.

See also

• List of medical roots, suffixes and prefixes
• Neoclassical compound – Compound words composed from Latin or ancient Greek