Study Rationale:
Organovo will leverage its tools and expertise as a 3D biology company to construct a lung model suitable for the screening of certain pharmaceutical compounds. Robust lab-based lung tissue models may serve as a valuable alternative to expensive testing in pre-clinical models and avoid the pitfalls commonly associated with extrapolating from models to humans.
Hypothesis:
We hypothesize that stable, in vitro models of lung that retain key cell types will respond to certain pharmaceutical agents with responses that can be measured biochemically and at the cellular level.
Study Design:
Major complexities that make the lung particularly challenging to model include the fine airway structures, the numerous types of cells and mass to space ratios. We will begin in a manual format with various mixtures of a subset of these cell types and seek to form simple organization and structures that are reminiscent of, but not exactly like the organization and structures present in the normal human lung. When simple functionality is obtained as determined by the production of lung-specific materials, then screening with specific pharmaceutical compounds will be carried out. Once basic cellular features are demonstrated in the optimized design, more complex 3D structures with enhanced precision and reproducibility will be generated with 3D bioprinting technology.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Robust and reproducible human lung tissue models have the potential to improve both the speed and cost of drug discovery and development. Of particular note is the likely improvement in predictive capability over pre-clinical models, which often correlate poorly with human outcomes.
Next Steps for Development:
Validation of model human lung tissue would be the follow-up step once viable candidates are realized. It is envisioned that therapeutic compounds with known human effects (for control) and then unknown agents will be screened on these lab-based models of human lung tissue.