Fibroblastic Colony‐Forming Unit Bone Marrow Cells Delay Progression to Gastric Dysplasia in a Helicobacter Model of Gastric Tumorigenesis

Bone marrow mesenchymal stem cells (MSCs) have been shown to have immune modulatory effects. Despite efforts to identify these cells in vivo, to date, MSCs have been defined mainly by their in vitro cell characteristics. Here, we show that Lin − CD44 hi Sca1 − cKit + CD34 − cells make up ∼0.5%–1% of murine whole bone marrow cells and yield nearly an equal amount of fibroblastic colony‐forming units (CFU‐F) as whole bone marrow. After transplantation into lethally irradiated recipients, Lin − CD44 hi Sca1 − cKit + CD34 − cells engrafted in the bone marrow long‐term and demonstrated characteristics of MSCs, including capacity to differentiate into osteoblasts and adipocytes. To examine whether Lin − CD44 hi Sca1 − cKit + CD34 − cells have immune modulatory effects, in vitro coculture with activated CD4+ T‐cells resulted in decreased Th17 cell differentiation by Lin − CD44 hi Sca1 − cKit + CD34 − cells. Furthermore, serial infusions with Lin − CD44 hi Sca1 − cKit + CD34 − cells reduced the progression to low‐grade gastric dysplasia in mice infected with chronic Helicobacter felis ( p = .038). This correlated with reduced gastric interleukin (IL)‐17F, IL‐22, and ROR‐γt gene expression in responding mice ( p < .05). These data suggest that bone marrow derived Lin − CD44 hi Sca1 − cKit + CD34 − cells have characteristics of MSCs and reduce progression of early gastric tumorigenesis induced by chronic H. felis infection. The prevention of dysplastic changes may occur through inhibition of Th17‐dependent pathways. STEM CELLS 2009;27:2301–2311