Scientists at Beth Israel Deaconess Medical Center, Harvard Medical School, Massachusetts Institute of Technology in Boston and The University of Texas MD Anderson Cancer Center in Houston have identified 4 four sources of cells which drive fibrosis. Fibrosis occurs in organs such as the lungs, liver, and kidneys, and is caused by excessive functioning of collagen to connect damaged tissue, resulting in inflammation, hardening organs, and cancer. The study has been published online at Nature Medicine on June 30.
In this study, researchers utilized mouse models with the gene-causing kidney fibrosis and employed a fate-mapping strategy to track cells on their way to becoming myofibroblasts. In fate mapping, the promoter of a protein expresses a color inside a cell that remains with the cell no matter what happens to it until it dies.
As a result, the researchers identified four sources of cells called myofibroblasts, the dominant producers of collagen. This was particularly important because two of the four sources of myofibroblasts start out as another cell type and differentiate into the collagen-producing cells. All myofibroblasts were produced: 50% by the proliferation of pre-existing resting fibroblasts, 35% by mesenchymal stem cells which originate in the bone marrow, 10% by endothelial to mesenchymal transition in which blood vessel cells change into mesenchymal cells, and 5% by epithelial to mesenchymal transition in which functional cells of an organ behave like mesenchymal cells.
“Answering a fundamental question about the origin of these cells by identifying four separate pathways involved in their formation allows us to look at ways to block those pathways to treat fibrosis,” said senior author Raghu Kalluri, Ph.D., M.D., MD Anderson chair and professor of Cancer Biology. “In addition to being lethal in its own right, fibrosis is a precursor for the development of cancer and plays a role in progression, metastasis and treatment resistance. In some cancers, such as pancreatic cancer, up to 95 percent of tumors consist of fibrotic stroma.”