Table 3.
Decision framework for CCM model selection
| Research question | Recommended model | Key readouts | References |
|---|---|---|---|
| Early signaling (MEKK3-KLF2/4, Rho/ROCK) | 2D iPSC-ECs, iVECs | qPCR/RNA-seq (KLF2/4, RhoA), WB (p-MLC2), IF (stress fibers) | [46, 58] |
| Barrier function & junctional integrity | BBB organoids |
TEER(> 200 Ω·cm²), FITC-dextran permeability, IF (CLDN5, ZO-1) |
[65, 67, 80] |
| EndMT & phenotypic switching | Vascular organoids, 2D co-culture |
IF/flow cytometry (α-SMA, CD31 loss), qPCR (SNAIL1/2, TGF-β targets) |
[81, 82] |
|
Multi-cellular interactions (EC-pericyte-astrocyte) |
BBB organoids + vascular organoids |
Live imaging (vascular sprouting), scRNA-seq (cell state transitions) |
[66, 67] |
| Microenvironment & flow effects | Organoids-on-chip (µfluidics) | Permeability tracers under shear, spatial transcriptomics | [83, 84] |
| Clonal expansion & mosaicism | Mixed population organoids + lineage tracing |
Barcoding/scRNA-seq (clone size), live imaging (proliferation) |
[22, 85] |