Bone marrow contributions to fibrosis

Abstract

Bone marrow transplant experiments in mice using labelled donor bone marrow have indicated that following injury bone marrow derived cells can circulate and home to the injured organs. In particular fibrocytes and myofibroblasts are capable of contributing to the wound healing response, including collagen deposition. In chronic injury this can lead to a pathological degree of fibrosis. Experiments have shown that this can be a relatively insignificant contribution to the scar forming population in certain organs and that the majority of the scar forming cells are intrinsic to the organ. Conversely, in certain circumstances, the circulating cells become major players in the organs fibrotic response. Whilst cell tracking experiments are relatively simple to perform, to actually determine a functional contribution to a fibrotic response more sophisticated approaches are required. This can include the use of bone marrow transplantation from recipients with collagen reporter systems which gives a read out of bone marrow derived cells that are transcriptional active for collagen production in a damaged organ. Another technique is to use bone marrow transplants from donors that have a mutation in the collagen to demonstrate a functional difference in fibrosis when bone marrow transplants performed. Recent reports have identified factors mediating recruitment of circulating fibrocytes to injured organs, such as CXCL12 and CXCL16 and shown that blocking these factors reduced fibrocyte recruitment and subsequent fibrosis. The identification of such factors may enable the development of novel therapies to block further fibrocyte engraftment and fibrosis in situations of pathological scarring. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease.