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Biomechanical Strain Exacerbates Inflammation on a Progeria-on-a-Chip Model
João Ribas1,2,3, Yu Shrike Zhang1,2, Patrícia R Pitrez4,5
1Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA.
Small (Weinheim an Der Bergstrasse, Germany)
|February 18, 2017
Summary
A new progeria-on-a-chip model reveals that biomechanical strain exacerbates vascular aging in Hutchinson-Gilford progeria syndrome (HGPS) by increasing inflammation and DNA damage in smooth muscle cells. Drug intervention reversed these effects.
Area of Science:
- Biomedical Engineering
- Vascular Biology
- Regenerative Medicine
Background:
- Organ-on-a-chip platforms mimic human organ microenvironments for disease modeling.
- Hutchinson-Gilford progeria syndrome (HGPS) causes premature vascular aging and cardiovascular disease.
- Vascular cells in HGPS are susceptible to mechanical stress.
Purpose of the Study:
- To develop a progeria-on-a-chip model for studying vascular aging in HGPS.
- To investigate the impact of biomechanical strain on HGPS vascular cells.
- To explore therapeutic interventions for HGPS-related vascular dysfunction.
Main Methods:
- Engineered microfluidic devices to model vascular tissue.
- Utilized smooth muscle cells (SMCs) from HGPS patients and healthy donors.
- Applied physiological and pathological biomechanical strain.
- Analyzed inflammatory markers, DNA damage, and gene expression.
- Tested pharmacological interventions.
Main Results:
- Pathological strain induced a hypertensive phenotype in SMCs.
- HGPS-derived iPS-SMCs showed exacerbated inflammation and DNA damage under strain compared to healthy controls.
- Strain-induced damage was reversed by pharmacological treatment, shifting gene expression away from inflammation.
Conclusions:
- The progeria-on-a-chip model effectively simulates biomechanical effects in vascular aging and HGPS.
- Biomechanical strain significantly contributes to vascular pathology in HGPS.
- This platform aids in discovering therapeutic targets and drugs for HGPS vascular disease.
