Intestinal organoids are grown from Lgr5+ stem cells embedded in a Matrigel dome, forming a hollow epithelial cyst around a central lumen. Proliferation follows logistic growth toward a carrying capacity set by nutrient and space limits.
The forskolin-induced swelling (FIS) assay is a real diagnostic and drug-testing tool for cystic fibrosis: forskolin raises cAMP, which opens CFTR chloride channels, driving fluid into the lumen and swelling the organoid. Loss-of-function CFTR mutations blunt swelling; CFTR-modulator drugs (correctors/potentiators) can partially restore it, which is exactly how patient-derived organoids are used to predict individual drug response.
dN/dt = k·N·(1 − N/N_max) (proliferation)
R_base = sqrt(N·A_cell / 4π) (monolayer shell radius)
CFTR_active = G + (100−G)·D^1.5/(EC50^1.5+D^1.5)
dR_swell/dt = k_sw·(CFTR_active/100)·forskolin − k_decay·R_swell
- Proliferation rate — division constant k (cells/day) in the logistic growth model, sets how fast the organoid expands toward N_max = 420 cells.
- CFTR genotype function (G) — baseline channel activity from 0% (severe loss-of-function mutant, e.g. F508del/F508del) to 100% (wild type).
- CFTR-modulator dose (D) — a corrector/potentiator drug; its rescue follows a Hill dose-response curve with EC50 = 30 µM.
- Forskolin — toggles the cAMP stimulus that drives fluid secretion into the lumen; swelling only occurs while it's on and CFTR is active.
This mirrors how labs screen CFTR modulators: patient organoids with defective CFTR barely swell under forskolin, but swell increasingly as effective drug doses are added — a direct, quantifiable readout of drug efficacy per patient genotype.