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Infarct Fibroblasts Do Not Derive From Bone Marrow Lineages

Thomas Moore-Morris1, Paola Cattaneo1, Nuno Guimarães-Camboa1

  • 1From the Aix Marseille Univ, INSERM, UMR_S910, GMGF, France (T.M.-M., M.P.); Skaggs School of Pharmacy and Pharmaceutical Sciences (P.C., N.G.-C., L.Z., S.M.E.), Department of Medicine (J.B., Y.G., N.D.D., K.L.P., J.C., S.M.E.), and Department of Pharmacology (I.B., S.M.E.), University of California at San Diego, La Jolla; National Research Council, Institute of Genetics and Biomedical Research, Milan Unit, Italy (P.C.); Humanitas Clinical and Research Center, Rozzano (MI), Italy (P.C.); and Cardiovascular Development and Repair Department, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (M.C., M.R.).

Circulation Research
|December 23, 2017
PubMed

Insights

Cardiac fibroblasts forming scars after myocardial infarction primarily originate from the epicardium, not bone marrow. This study clarifies fibroblast origins in heart attack scar tissue.

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.
Abstract

Keywords:
bone marrowfibroblastsfibrosisheart diseasesmyocardial infarction

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