Infarct Fibroblasts Do Not Derive From Bone Marrow Lineages.

Area of Science:

• Cardiovascular Biology
• Regenerative Medicine
• Fibrosis Research

Background:

• Myocardial infarction (MI) is a leading cause of mortality.
• The cellular origins of cardiac fibroblasts in the post-MI scar are debated.
• A potential contribution from bone marrow lineages to scar fibroblasts is a key question.

Purpose of the Study:

• To determine the origin of cardiac fibroblasts in the infarct scar.
• To investigate the role of bone marrow and hematopoietic lineages in fibroblast formation.
• To utilize lineage tracing and a Collagen1a1-green fluorescent protein reporter for robust identification.

Main Methods:

• Genetic lineage tracing in mouse models.
• Bone marrow transplantation experiments.
• Permanent left anterior descending coronary artery ligation to induce myocardial infarction.
• Analysis of Collagen1a1-green fluorescent protein expression.

Main Results:

• No evidence of collagen-producing fibroblasts originating from hematopoietic or bone marrow lineages was found post-MI.
• The majority of fibroblasts within the infarcted area were identified as being of epicardial origin.
• Collagen-producing fibrocytes from hematopoietic lineages were observed on the epicardial surface, potentially related to surgical procedures.

Conclusions:

• The predominant source of infarct fibroblasts is the epicardium, not bone marrow or blood.
• Endothelial-to-mesenchymal transition is not a significant source of these fibroblasts.
• Surgical manipulation may contribute to the presence of fibrocytes on the epicardial surface.