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Peer-reviewedCC BY-NCScience Advances

Human trilayer engineered blood vessel reveals influence of fibroblasts on disease progression in model of Hutchinson-Gilford progeria

  • Kevin L. Shores1
  • Xin D. Gao2,3,4
  • David R. Liu2,3,4
  • George A. Truskey1
4 affiliations
  1. 1Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
  2. 2Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  3. 3Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
  4. 4Howard Hughes Medical Institutes, Harvard University, Cambridge, MA 02138, USA.
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Abstract

In vitro models of vascular disease have focused primarily on the pathophysiology of smooth muscle cell (SMC) or endothelial cell (EC). 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 trilayer tissue-engineered blood vessels (TEBVs) with SMCs, ECs, and fibroblasts. 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. By generating TEBVs with different combinations of vascular cells with or without the HGPS mutation, we found that fibroblasts contributed to extracellular matrix dysregulation and fibrotic signaling, SMCs to collagen accumulation, and ECs to inflammation. These results clarify the poorly understood influence of fibroblasts in progression of HGPS vascular pathology. The trilayer TEBV model could enable further mechanistic insights or therapeutic discovery for other vascular diseases.

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Cite

BibTeXRIS
BibTeX
@article{shores2026human,
  title = {{Human trilayer engineered blood vessel reveals influence of fibroblasts on disease progression in model of Hutchinson-Gilford progeria}},
  author = {Kevin L. Shores and Xin D. Gao and David R. Liu and George A. Truskey},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aeh3785},
  url = {https://www.science.org/doi/10.1126/sciadv.aeh3785},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Human trilayer engineered blood vessel reveals influence of fibroblasts on disease progression in model of Hutchinson-Gilford progeria
AU  - Kevin L. Shores
AU  - Xin D. Gao
AU  - David R. Liu
AU  - George A. Truskey
PY  - 2026
DA  - 2026/10/09
JO  - Science Advances
DO  - 10.1126/sciadv.aeh3785
UR  - https://www.science.org/doi/10.1126/sciadv.aeh3785
AB  - In vitro models of vascular disease have focused primarily on the pathophysiology of smooth muscle cell (SMC) or endothelial cell (EC). 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 trilayer tissue-engineered blood vessels (TEBVs) with SMCs, ECs, and fibroblasts. 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. By generating TEBVs with different combinations of vascular cells with or without the HGPS mutation, we found that fibroblasts contributed to extracellular matrix dysregulation and fibrotic signaling, SMCs to collagen accumulation, and ECs to inflammation. These results clarify the poorly understood influence of fibroblasts in progression of HGPS vascular pathology. The trilayer TEBV model could enable further mechanistic insights or therapeutic discovery for other vascular diseases.
SN  - 2375-2548
ER  -