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Updated: Mar 17, 2026
Isolation and Characterization of Adult Cardiac Fibroblasts and Myofibroblasts
Published on: March 12, 2020
Genetic lineage tracing defines myofibroblast origin and function in the injured heart
Onur Kanisicak1, Hadi Khalil1, Malina J Ivey2
1Department of Pediatrics and Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Insights
Cardiac myofibroblasts, crucial for heart healing and fibrosis, originate from tissue-resident fibroblasts. Targeting these periostin-expressing cells impacts scar formation and promotes adaptive healing after myocardial infarction.
Area of Science:
- Cardiovascular Biology
- Cellular Biology
- Fibrosis Research
Background:
- Myofibroblasts are key in cardiac repair after injury and in chronic fibrotic disease.
- The precise origin and in vivo functions of myofibroblasts remain incompletely understood.
Purpose of the Study:
- To identify the cellular origins of cardiac myofibroblasts.
- To investigate the role of myofibroblasts in myocardial infarction (MI) healing and fibrosis.
Main Methods:
- Generation of Postn (periostin) gene-targeted mice with inducible Cre for lineage tracing.
- Utilizing four additional Cre-expressing mouse lines for comprehensive cell tracing.
- Assessing collagen production and scar formation post-MI following myofibroblast deletion.
Main Results:
- Periostin-expressing myofibroblasts in the heart originate from Tcf21 lineage fibroblasts, not other cell types.
- Deletion of periostin-expressing myofibroblasts significantly reduces collagen production and scar size after MI.
- Myofibroblasts identified by periostin tracing can revert to a less-activated state after injury resolution.
Conclusions:
- Cardiac myofibroblasts are defined as periostin-expressing cells essential for adaptive healing and fibrosis.
- These myofibroblasts arise from Tcf21-positive tissue-resident fibroblasts.
- Targeting periostin-expressing myofibroblasts offers a potential therapeutic strategy for cardiac repair.
Abstract:
Cardiac fibroblasts convert to myofibroblasts with injury to mediate healing after acute myocardial infarction (MI) and to mediate long-standing fibrosis with chronic disease. Myofibroblasts remain a poorly defined cell type in terms of their origins and functional effects in vivo. Here we generate Postn (periostin) gene-targeted mice containing a tamoxifen-inducible Cre for cellular lineage-tracing analysis. This Postn allele identifies essentially all myofibroblasts within the heart and multiple other tissues. Lineage tracing with four additional Cre-expressing mouse lines shows that periostin-expressing myofibroblasts in the heart derive from tissue-resident fibroblasts of the Tcf21 lineage, but not endothelial, immune/myeloid or smooth muscle cells. Deletion of periostin(+) myofibroblasts reduces collagen production and scar formation after MI. Periostin-traced myofibroblasts also revert back to a less-activated state upon injury resolution. Our results define the myofibroblast as a periostin-expressing cell type necessary for adaptive healing and fibrosis in the heart, which arises from Tcf21(+) tissue-resident fibroblasts.
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