Organoid Models Derived from Intestinal Stem Cells for Disease Modelling
DOI:
https://doi.org/10.5281/zenodo.22274620Keywords:
Intestinal organoids; Intestinal stem cells; Disease modelling; Cystic fibrosis; Colorectal cancerAbstract
Background: Intestinal organoids grown from Lgr5-positive stem cells reproduce crypt-villus architecture and regional
identity, but contain epithelium alone, without immune cells, fibroblasts, neurons or vasculature.
Objective: To assess where organoid disease modelling is strong and where it is weaker, from culture chemistry to the
clinical programmes built on an organoid readout.
Methods: Narrative review of derivation studies, infection models, tumour biobanks and prospective trials.
Findings: Cultures from needle biopsies of metastatic colorectal cancer succeeded in 71% of attempts across 14 patients,
copy-number profiles correlating at r = 0.89. In the SENSOR trial, 31 cultures came from 54 eligible patients and none of six
treated patients responded. In 34 infants with cystic fibrosis, forskolin-induced swelling correlated with sweat chloride at r =-0.82.
Conclusions: The evidence supports organoids for mechanism and infection biology, and a functional readout of the causal
defect in cystic fibrosis, but not chemosensitivity testing for drug choice.
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