Cited by 551Cellular Mechanics and InteractionsTissue Engineering and Regenerative MedicineElasticity and Material Modeling

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Targeting extracellular matrix stiffness to attenuate disease: From molecular mechanisms to clinical trials

Lampi, Marsha C., Reinhart-King, Cynthia A.·2018·Science Translational Medicine

DOI 10.1126/scitranslmed.aao0475

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Abstract

Tissues stiffen during aging and during the pathological progression of cancer, fibrosis, and cardiovascular disease. Extracellular matrix stiffness is emerging as a prominent mechanical cue that precedes disease and drives its progression by altering cellular behaviors. Targeting extracellular matrix mechanics, by preventing or reversing tissue stiffening or interrupting the cellular response, is a therapeutic approach with clinical potential. Major drivers of changes to the mechanical properties of the extracellular matrix include phenotypically converted myofibroblasts, transforming growth factor β (TGFβ), and matrix cross-linking. Potential pharmacological interventions to overcome extracellular matrix stiffening are emerging clinically. Aside from targeting stiffening directly, alternative approaches to mitigate the effects of increased matrix stiffness aim to identify and inhibit the downstream cellular response to matrix stiffness. Therapeutic interventions that target tissue stiffening are discussed in the context of their limitations, preclinical drug development efforts, and clinical trials.

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Authors: Lampi, M. C., & Reinhart-King, C. A.
Affiliations: Cornell University (US)
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37212, USA.
ORCID: Lampi, Marsha C.
Reinhart-King, Cynthia A.
Venue: Science Translational Medicine
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2018-01-03
Volume: 10
Issue: 422
ISSN: 1946-6234 (ISSN-L)
1946-6242
DOI: 10.1126/scitranslmed.aao0475
OpenAlex: W2781877987
Cited by: 551
References: 159
Citations by year: 2026: 50 · 2025: 68 · 2024: 57 · 2023: 77 · 2022: 81 · 2021: 69 · 2020: 72 · 2019: 43 · 2018: 32
FWCI: 6.09
Type: journal article
Language: en
Open access: closed
Locations: Science Translational Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: National Science Foundation (award333523, 1435755, award333525, 2013155462)
Ford Foundation (award333526)
National Heart, Lung, and Blood Institute (award333524, HL127499)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Physical Sciences › Engineering › Biomedical Engineering › Elasticity and Material Modeling
Keywords: extracellular matrix stiffness, tissue stiffening, mechanotransduction, myofibroblasts, TGF-beta, tumor progression, fibrosis, cardiovascular disease, aging, pharmacological interventions, drug development, clinical trials
MeSH terms: Animals, Cell Differentiation, Extracellular Matrix, Fibrosis, Humans, Transforming Growth Factor beta, Myofibroblasts

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Targeting extracellular matrix stiffness to attenuate disease: From molecular mechanisms to clinical trials

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