Human tri-layer engineered blood vessel reveals influence of fibroblasts on disease progression in model of Hutchinson-Gilford Progeria Syndrome

Adventitial fibroblasts can contribute to disease progression, but their specific influence is not well understood in different disease contexts. To elucidate fibroblast’s impact on vascular pathology, we developed patient-specific, tri-layer tissue-engineered blood vessels (TEBVs) with SMCs, ECs, and fibroblasts.

Using bi-layer (SMCs and ECs) and tri-layer TEBVs, we modeled atherosclerosis in the accelerated aging disease, Hutchinson-Gilford Progeria Syndrome (HGPS). HGPS fibroblasts substantially elevated several features of the vascular pathology. Correcting the HGPS-associated mutation using base editing returned many disease characteristics to healthy levels.