In cell biology, a common approach has been to seed cells on 2D culture dishes.
The method is simple and highly reproducible, but it is also a simplified model.
As a result, it has clear limitations for studying complex phenomena that better reflect intact tissues and organs.
Against this backdrop, organoid culture has become increasingly popular.
However, many of its drawbacks are, in a sense, the other side of 2D culture’s strengths: organoids are more complex and harder to keep stable.
Broadly speaking, organoid research brings together stem cell biology and tissue regeneration.
Because it depends on cell–cell adhesion and self-organization, it can be harder to design experiments and get consistent, easy-to-interpret readouts.
In addition, organoid culture can place cells under stresses that are less common in vivo.
To reduce these stresses, a variety of strategies have been developed.
Common examples include:
- oxidative stress (including ROS-related stress)
- hypoxic stress
- endoplasmic reticulum (ER) stress
- mechanical stress imposed by the extracellular matrix (ECM)
Reducing these stresses remains a major challenge in organoid culture.
Organoids contain clustered cells, but unlike in vivo tissue, they lack blood flow.
Because nutrients and oxygen are delivered mainly by diffusion, concentration gradients can easily form depending on the distance from the surrounding medium.
As a result, apoptosis can occur in the core and then spread, potentially driven by signals such as cell debris.
To address this, a range of culture formats has been developed—for example, perfusion culture systems and air–liquid interface (ALI) culture.
In my view, regardless of the method, the workflow needs to be reasonably easy to run.
Otherwise, it becomes difficult to get consistent results, and the technique still feels incomplete.
The views expressed here are solely my own. This text was drafted by the author and subsequently edited for clarity with the assistance of an AI tool.
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