Cell culture investigations using spheroids and organoid models have had a major impact on biomedical advancement as alternative sources for costly, in vivo animal testing. However, these 3-D cell constructs are limited in that they do not integrate extracellular components within the structure important for more reliable and accurate biological responses. Extracellular matrix (ECM) from decellularized tissues provide a physical scaffolding and offers crucial biochemical and biomechanical cues for cellular constituents. Current spheroid and/or organoid 3D culture platforms only surround the cell structure with ECM, if ECM components are included at all. Therefore, these current models: (1) do not reflect the complexity of an in vivo micro-environment, (2) don’t provide signaling ligands for cells where they reside and (3) don’t provide standardizable models for 3D cell-based research.
The current invention describes a novel method to create compact, self-contained spheroid integrating both cells and tissue ECM-dense regions within the spheroid – superior to traditional, cell-only spheroids. The method promotes integration with fibroblasts and macrophages after cells are assembled with decellularized tissue ECM. The results suggest incorporating decellularized tissue ECM within a spheroid offers an improved ex vivo tumor microenvironment influencing cancer phenotype in cell invasion and migration. The usage of decellularized tissue ECM in this technology offers a relatively standardizable, reproducible and valuable tool for drug discovery and diagnostic purposes. It provides accurate assessment of cell behavior and response to perturbation in an in vivo microenvironment.
The technology is available licenseng and collaboration opportunities to interested entities.
- Self-assembled spheroid integrating both cell and ECM dense regions – rather than cell-only spheroids
- Inclusion of compositionally complex decellularized tissues – rather than isolated components (e.g., Laminin)
- Only self-assembling ECM/cell spheroid preserving complexity of tissue microenvironment
- Standardizable method for tissue type-specific, 3D culture reconstitution
- Easily scaled-up for high throughput drug discovery and diagnostic purposes
- Personalized medicine diagnostic tool for patient-specific drug screening
- Development of companion diagnostics
- In vitro platform for high-throughput screening of novel cancer compounds and immunotherapy
- In vitro 3D modeling of microenvironment for other types of disease
- Constructs for cell delivery