Hematopoietic origins of fibroblasts: I. In vivo studies of fibroblasts associated with solid tumors

ObjectiveRecent studies have reported that bone marrow cells can give rise to tissue fibroblasts. However, the bone marrow cell(s) that gives rise to fibroblasts has not yet been identified. In the present study, we tested the hypothesis that tissue fibroblasts are derived from hematopoietic stem cells (HSCs) in vivo.MethodsThese studies were conducted using mice whose hematopoiesis had been reconstituted by transplantation of a clonal population of cells derived from a single enhanced green fluorescent protein (EGFP)-positive HSC in conjunction with murine tumor models.ResultsWhen tumors propagated in the transplanted mice were evaluated for the presence of EGFP+ HSC-derived cells, two prominent populations of EGFP+ cells were found. The first were determined to be fibroblasts within the tumor stromal capsule, a subset of which expressed type I collagen mRNA and α-smooth muscle actin. The second population was a perivascular cell associated with the CD31+ tumor blood vessels.ConclusionThese in vivo findings establish an HSC origin of fibroblasts.