Organoids
Organoids are 3D structures that typically range from approximately 100 μm (e.g. lung organoids) to 2 mm (e.g. brain organoids). They are derived from induced pluripotent stem cells (iPSCs), adult stem cells, or somatic cells that self-assemble and differentiate to form 3D structures that mimic both the architecture and cellular composition of human tissue. Self-assembly is guided by a specific cocktail of growth factors added to the cell culturing media or to the ECM, which provides a scaffold for tissue growth, closely mimicking the in vivo environment. Tumoroids are specialised organoids, formed by patient-derived cancer cells.
Courtesy of Prof. Jens Schwamborn
Organoid Applications
- Basic research and early drug discovery: Suitable for investigating cellular biology, interaction and crosstalk, drug mechanisms, and drug responses (including personalised treatments).
- Disease modelling: Valuable for studying disease mechanisms and identifying potential therapeutic targets in areas such as cancer, genetic disorders, rare diseases, and infectious diseases.
- Drug screening: Provide a system for testing drug efficacy and toxicity, and predictions of drug metabolism and clearance (ADME).
- Personalised medicine: Enable testing of how individual patients (considering factors like sex, age, and ethnicity) respond to specific treatments, allowing for more personalised therapeutic strategies.
Organoid Advantages
- Improved biomimicry: Replicate the physiological behaviours, cellular heterogeneity, gene expression, and structural architecture of human tissues better than 2D cultures.
- Complex cellular composition: Contain multiple functionally relevant cell lineages, allowing them to mimic organs and tissues more accurately than spheroids.
- Self-renewal and longevity: Can be cultivated over extended periods while retaining their stemness, allowing for long-term studies.
- High-throughput capabilities: Can be used in high-throughput studies and screening applications.
- Personalised medicine potential: Can be generated from a patient’s own tissues, aiding in the development of personalised treatments tailored to individual responses.
Organoid Limitations
- Lack of mechanical stimulation: Do not receive the mechanical stimuli (e.g. substrate strain, fluid shear stress, and hydrostatic pressure) crucial for regulating cell development and behaviour.
- Access challenges: Form closed structures as the epithelium is facing inwards, making direct experimental access to the lumen difficult and many studies very challenging (e.g. microbiome and infection studies).
- Reproducibility issues: Low reproducibility and variability between organoids derived from the same source can affect the consistency of results.
- Maturation limitations: Not suitable for tissues that require differentiation at an air-liquid interface and iPSC-derived organoids may not mature beyond a foetal phenotype unless grafted into living organisms, which can limit physiological relevance.
- Resource intensive: Setting up organoid cultures can be time-consuming and expensive due to the need for specialised equipment and materials.