Researchers have engineered a fully human microphysiological system that replicates the vascular malformations caused by Hereditary Hemorrhagic Telangiectasia, Nature Communications reported on August 13, 2026.
Hereditary Hemorrhagic Telangiectasia (HHT) is a rare congenital condition marked by fragile vascular malformations that develop focally across multiple organs. Patients inherit loss-of-function mutations that affect Alk1-Eng signaling, but how this manifests as vascular malformations remains poorly understood. Current clinical options remain scarce, and the disease has no cure.
The team designed a perfused vascular platform using primary endothelial cells. Inside the chip, inducible shRNA controls endogenous Alk1 expression. The resulting vascular malformations developed over several days and reproduced the physical appearance of patient lesions. The platform demonstrated that only a subpopulation of Alk1-deficient endothelial cells is necessary to trigger malformation growth.
Single-cell transcriptomic analysis indicated that microvessel pruning and vessel regression both contribute to malformation development. The researchers also observed a loss of PDGFB, pointing to a role for mural cell recruitment in the disease process. When the team applied pharmacological VEGF and VEGFR inhibitors, the treatment blocked lesion formation within the chip.
Investigators from the University of California-Irvine, Tulane University, and the Louisiana Cancer Research Center conducted the study. Co-authors Christopher C. W. Hughes and Abraham P. Lee hold equity interests in Aracari Biosciences, Inc., a company commercializing a vascularized microtumor model. Funding sources included the National Institutes of Health, the Department of Defense, and the National Science Foundation.
