A fibroblast is not always just a fibroblast – particularly in the heart.
In a heart attack, fibroblasts – special repair cells that form a scar after injury – come from a population of stem cells that reside within the heart, said researchers from Baylor College of Medicine and the Methodist Hospital in a report that appears in the journal Cardiovascular Research. By contrast, earlier work showed that the fibroblasts responsible for fibrosis – excess fibrous connective tissue – found in cardiomyopathy or heart failure came from a special kind of white blood cell called a monocyte, which originates in the bone marrow.
The finding has implications for the treatment of heart failure, said Dr. Mark Entman, chief of the division of cardiovascular sciences in the Department of Medicine at BCM and the paper's corresponding author.
"The formation of poor scars that do not heal the heart after heart attack coexist with too much interstitial fibrosis," said Entman. "This new knowledge about the source of the fibroblast allows us to intervene in one process without harming the other."
"This work is important because it shows that the scar-forming fibroblasts come from precursor cells in the heart whereas our first paper showed that the fibroblast precursors coming from the bone marrow cause cardiomyopathy. Understanding this may help us limit fibrosis caused by cells coming from the bone marrow without affecting the scar-forming fibroblasts you need to heal after a heart attack," said Dr. Signe Carlson, who did much of the work in the study as a graduate student in the department of biochemistry and molecular biology and is the report's first author.
These mesenchymal stem cells exist normally as a small population of cells within the heart. Signals from a heart attack activate them to rush to the site of tissue injury within 36 hours and differentiate into fibroblasts. Other signals can drive the stem cells to differentiate into various kinds of cells in vitro, including osteocytes (bone cells), adipocytes (fat cells) and chondrocytes (cartilage cells)
Stem cells rush to site
In experiments in cells in the laboratory and in mice, Entman, Carlson and their colleagues showed that this special population of stem cells massed at the site of the heart attack injury within hours. They also confirmed that the population of cells they were studying had all the characteristics of stem cells and could become fibroblasts.
Without the inflammation that drives the stem cells to differentiate into fibroblasts to form a strong scar after a heart attack, the hearts would literally rupture, said Entman.
Others who took part in this work include Drs. JoAnn Trial of BCM and Dr. Christian Soeller of the School of Medical Sciences at the University of Auckland in New Zealand.
Funding for this work came from the National Institutes of Health and the National Science Foundation.