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

Exp Hematol. 2006 Feb;34(2):208-18. doi: 10.1016/j.exphem.2005.10.009.

Abstract

Objective: Recent 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.

Methods: These 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.

Results: When 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 alpha-smooth muscle actin. The second population was a perivascular cell associated with the CD31(+) tumor blood vessels.

Conclusion: These in vivo findings establish an HSC origin of fibroblasts.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Line, Tumor
  • Clone Cells
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Gene Expression Regulation, Neoplastic
  • Green Fluorescent Proteins / metabolism
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / blood supply
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Stromal Cells / pathology
  • Transplantation, Homologous
  • Tumor Cells, Cultured
  • Whole-Body Irradiation

Substances

  • Actins
  • Collagen Type I
  • Platelet Endothelial Cell Adhesion Molecule-1
  • RNA, Messenger
  • collagen type I, alpha 1 chain
  • Green Fluorescent Proteins