Gastritis promotes an activated bone marrow-derived mesenchymal stem cell with a phenotype reminiscent of a cancer-promoting cell

Dig Dis Sci. 2014 Mar;59(3):569-82. doi: 10.1007/s10620-013-2927-z. Epub 2013 Nov 8.


Background: Bone marrow-derived mesenchymal stem cells (BM-MSCs) promote gastric cancer in response to gastritis. In culture, BM-MSCs are prone to mutation with continued passage but it is unknown whether a similar process occurs in vivo in response to gastritis.

Aim: The purpose of this study was to identify the role of chronic gastritis in the transformation of BM-MSCs leading to an activated cancer-promoting phenotype.

Methods: Age matched C57BL/6 (BL/6) and gastrin deficient (GKO) mice were used for isolation of stomach, serum and mesenchymal stem cells (MSCs) at 3 and 6 months of age. MSC activation was assessed by growth curve analysis, fluorescence-activated cell sorting and xenograft assays. To allow for the isolation of bone marrow-derived stromal cells and assay in response to chronic gastritis, IRG/Vav-1(Cre) mice that expressed both enhanced green fluorescent protein-expressing hematopoietic cells and red fluorescent protein-expressing stromal cells were generated. In a parabiosis experiment, IRG/Vav-1(Cre) mice were paired to either an uninfected Vav-1(Cre) littermate or a BL/6 mouse inoculated with Helicobacter pylori.

Results: GKO mice displayed severe atrophic gastritis accompanied by elevated gastric tissue and circulating transforming growth factor beta (TGFβ) by 3 months of age. Compared to BM-MSCs isolated from uninflamed BL/6 mice, BM-MSCs isolated from GKO mice displayed an increased proliferative rate and elevated phosphorylated-Smad3 suggesting active TGFβ signaling. In xenograft assays, mice injected with BM-MSCs from 6-month-old GKO animals displayed tumor growth. RFP+ stromal cells were rapidly recruited to the gastric mucosa of H. pylori parabionts and exhibited changes in gene expression.

Conclusions: Gastritis promotes the in vivo activation of BM-MSCs to a phenotype reminiscent of a cancer-promoting cell.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Proliferation
  • Cell Transformation, Neoplastic*
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / microbiology
  • Gastric Mucosa / pathology*
  • Gastrins / deficiency
  • Gastritis, Atrophic / metabolism
  • Gastritis, Atrophic / microbiology
  • Gastritis, Atrophic / pathology*
  • Hedgehog Proteins / metabolism
  • Helicobacter Infections / pathology
  • Helicobacter pylori
  • Immunoblotting
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Parabiosis
  • Phenotype*
  • Real-Time Polymerase Chain Reaction
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta / metabolism


  • Biomarkers
  • Gastrins
  • Hedgehog Proteins
  • Smad3 Protein
  • Smad3 protein, mouse
  • Transforming Growth Factor beta