An invited review following the Soujinkai Award: Human Induced Pluripotent Stem Cell Modeling of the Blood-Brain Barrier Identifies Intrinsic Barrier Dysfunction in Multiple Sclerosis

Blood-brain barrier (BBB) dysfunction found in the multiple sclerosis (MS) cases is generally considered as a consequence of neuroinflammation. In this study we challenge this view by developing and analyzing novel BBB model from MS patients using induced pluripotent stem cells (iPSCs). We differentiated iPSCs into brain microvascular endothelial cell (BMEC)-like cells to establish an in vitro BBB model. We found that BMEC-like cells from MS patients exhibited compromised barrier integrity, characterized by weakened junctions, heightened permeability, and an elevated inflammatory profile when compared to cells from healthy individuals. Notably, the activation of the Wnt/β-catenin signaling pathway led to improvements in barrier function and a reduction in inflammatory responses, indicating potential therapeutic targets for reinforcing BBB stability in MS.