1. ¹Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY, USA
2. ²Department of Medicine and Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA
3. ³Department of Surgery and Department of Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama
4. ⁴Division of Gastroenterology, Department of Internal medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Correspondence: Dr TC Wang, MD, Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, 1130 St. Nicholas Avenue, Room 925, 9th Floor, New York, NY, USA. E-mail: tcw21@columbia.edu

Received 25 December 2008; Revised 8 May 2009; Accepted 3 June 2009; Published online 19 October 2009.

Abstract

Recent studies with Helicobacter-infected mice have shown that bone marrow-derived cells can repopulate the gastric epithelium and progress to cancer. However, it has not been established which cellular subset can potentially contribute to the epithelium. The aim of this study was to investigate the ability of bone marrow-derived mesenchymal stem cells (MSCs) that express cytokeratin 19 (K19) to contribute to the gastric epithelium. MSCs cultures were established from whole bone marrow and expression of K19 was detected in a minority (1 of 13) of clones by real-time PCR and immunostaining. Transfection of a K19-green fluorescent protein (GFP) vector and isolation of GFP-expressing colonies generated high K19-expressing MSC clones (K19GFPMSC). Incubation of MSCs with gastric tissue extract markedly induced mRNA expression of gastric phenotypic markers and was observed to a greater extent in K19GFPMSCs compared with parental MSCs and mock transfectants. Both K19GFPMSCs and GFP-labeled control MSCs gave rise to gastric epithelial cells after injection into the murine stomach. In addition, after blastocyst injections, K19GFPMSCs gave rise to GFP-positive gastric epithelial cells in all 13 pups, whereas only 3 of 10 offspring showed GFP-positive gastric epithelial cells after injection of GFP-labeled control MSCs. Although K19 expression could not be detected in murine whole bone marrow, H. felis infection increased K19-expressing MSCs in the circulation. Taken together, our results show that bone marrow-derived MSCs can contribute to the gastric epithelium. The K19-positive MSC fraction that is induced by chronic H. felis infection appears to be the important subset in this process.