Patient-derived organoids and ex vivo models
An immortalised cell line has been selected for decades to grow in plastic. A patient-derived organoid still resembles the tumour it came from — including the parts that made it difficult.
01Why these models
Heterogeneity is the point
Patient-derived organoids retain much of the cellular heterogeneity and architecture of the tissue they were established from. That makes them a platform for testing therapeutic compounds and identifying treatment-predictive biomarkers in a patient-specific context, rather than in a cell line that stopped resembling any patient years ago.
For a discovery programme, that means efficacy signals that survive contact with primary tissue. For a translational programme, it means a bridge between a target and a patient population.
Systems established
Human colon organoids from surgical and biopsy specimens, including normal tissue and APC-mutated tissue from FAP patients, under IRB approval. Hormone-responsive 3D breast organoids from surgical reduction mammoplasty and fine-needle aspirate. Pancreatic neuroendocrine tumour organoids. 3D Matrigel culture of normal and malignant lines, with angiogenesis assays and quantitative readouts.
02Capability
What can be built and measured
- Primary tissue establishment from surgical and biopsy specimens, with the IRB framing to make it legitimate.
- Mouse mammary organ culture and a novel ex-vivo orthotopic model of human breast cancer, developed and published.
- Engineered lines — CRISPR knock-in and knock-out, lentiviral and retroviral transduction, conditional knockout and overexpression, drug-resistant line development.
- Readouts including EdU incorporation for proliferation, TUNEL for apoptosis, immunofluorescence and confocal imaging, and RNA-seq of treated organoids.
- Compound testing in a patient-specific context, with the statistical design to make the comparison meaningful.
03Track record
Models built and published
A novel and cost-effective ex vivo orthotopic model for the study of human breast cancer in mouse mammary gland organ culture — Biology Open, 2020, first author.
Butyrate-treated colon organoids from FAP subjects, with RNA-seq showing suppression of key cancer pathways when ZBP-89 is deleted — presented at Digestive Disease Week.
Generation and characterisation of human pancreatic neuroendocrine tumour organoids, with confocal and qPCR analysis.
—Also
Related capabilities
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