Biomechanical Strain Exacerbates Inflammation on a Progeria‐on‐a‐Chip Model
Abstract
Organ‐on‐a‐chip platforms seek to recapitulate the complex microenvironment of human organs using miniaturized microfluidic devices. Besides modeling healthy organs, these devices have been used to model diseases, yielding new insights into pathophysiology. Hutchinson‐Gilford progeria syndrome (HGPS) is a premature aging disease showing accelerated vascular aging, leading to the death of patients due to cardiovascular diseases. HGPS targets primarily vascular cells, which reside in mechanically active tissues. Here, a progeria‐on‐a‐chip model is developed and the effects of biomechanical strain are examined in the context of vascular aging and disease. Physiological strain induces a contractile phenotype in primary smooth muscle cells (SMCs), while a pathological strain induces a hypertensive phenotype similar to that of angiotensin II treatment. Interestingly, SMCs derived from human induced pluripotent stem cells of HGPS donors (HGPS iPS‐SMCs), but not from healthy donors, show an exacerbated inflammatory response to strain. In particular, increased levels of inflammation markers as well as DNA damage are observed. Pharmacological intervention reverses the strain‐induced damage by shifting gene expression profile away from inflammation. The progeria‐on‐a‐chip is a relevant platform to study biomechanics in vascular biology, particularly in the setting of vascular disease and aging, while simultaneously facilitating the discovery of new drugs and/or therapeutic targets.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 17, 2017
- Source ID
- 10.1002/smll.201603737
Entities
People
- Ali Khademhosseini
- Jeroen Leijten
- Jeroen Rouwkema
- João Ribas
- Lino Ferreira
- Mario Miscuglio
- Mehmet Remzi Dökmeci
- Patrícia R. Pitrez
- Xavier Nissan
- Yu Shrike Zhang
Organizations
- Defense Threat Reduction Agency
- French Muscular Dystrophy Association
- French National Institute of Health and Medical Research
- Harvard Medical School
- Harvard University
- King Abdulaziz University
- Konkuk University
- National Institutes of Health
- Office of Naval Research
- University of Coimbra
- University of Twente