3D Cell Cultures – Organoids, Spheroids and Tumoroids

The expansion of 3D cell cultures derived from tumor cells or excised biopsies offers tremendous advantages:

• Provides patterns of solid tumors
• Functions as specialized tool for genomics, epigenomic, pharmacologic, and biochemical studies
• Overcomes several limitations of traditional 2D cell models by revealing cell heterogeneity, intrinsic histologic structures, and cell-ECM communications

Presently, 3D models are extensively used as systems for studying various types of cancers: breast, colon, lung, pancreatic, cervical, and prostate. The substrate selected to culture and grow spheroids or organoids is a vital aspect in obtaining reproducible 3D cancer cell models.

• Spheroids 
• Organoids

Spheroids are well-designed cell aggregates used as engineered cancer models. They have the ability to boost the 3D construction of tumor growth to amplify tumor cell progression and to help reveal novel anti-cancer treatments. Tumor spheroids are able to meticulously reproduce the core properties of solid human tumors. They can be derived from cancer cell lines and may have the potential to function as mediators for 2D culturing models and for in vivo tissue xenografts. Tumor spheroids produced from permanent cancer cell lines are known to be avascular. They can induce micro-metastasis formation and have the potential to display cancer-like microenvironment features (e.g., cell-cell, cell-ECM exchanges, local nutrients transportation, gases, and growth factors).

Organoids are 3D-derived stem cell models, either from embryonic or adult stem cells. This type of organoid can exhibit self-regulation potential, phenotypic traits of the organ they are grown from, and physiological modeling of the environment through genomic alteration.

Pluripotent or organ-regulated stem cells can be helpful instruments to induce organoid growth. Furthermore, they can mimic the in vivo 3D architecture and have the capacity of multi-lineage differentiation of different types of tissues (e.g., designing airway organoids from lung-derived stem cell to study lung physiology, patterning, and lung morphogenesis).

In addition, cancer organoids or tumors-in-a-dish can be cultivated with high effectiveness (with high in vitro clonal propagation) from primary patient-derived normal or tumor masses and can support replication of a patient-specific phenotype. All these distinguishing features of cancer organoids (e.g., colorectal, pancreatic, prostate, and brain cancer organoids) enable approaches to study patient-unique drug responses.

Organoids limitations:

• Existing culturing techniques are not yet entirely developed to reconstruct the full biochemical and physical environment of the human body (e.g., brain organoid cells occasionally display gene expression differences from the cells they were planned to mimic)
• Lack of innervation, immune cells, or tumor stroma
• The lack of blood vessels restricts organoid dimensions and complexity

In summary, cancer organoids and tumor spheroids have the potential to be applied in many cancer-related fields, including drug discovery, toxicology, and disease modeling.