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Am J Physiol Gastrointest Liver Physiol 294: G778-G786, 2008. First published January 17, 2008; doi:10.1152/ajpgi.00468.2007
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MUCOSAL BIOLOGY

Topical transplantation of mesenchymal stem cells accelerates gastric ulcer healing in rats

Yujiro Hayashi,1 Shingo Tsuji,2 Masahiko Tsujii,2 Tsutomu Nishida,2 Shuji Ishii,2 Hideki Iijima,2 Toru Nakamura,1 Hiroshi Eguchi,1 Eiji Miyoshi,1 Norio Hayashi,2 and Sunao Kawano1,3

1Department of Clinical Laboratory Science and 2Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita; and 3Izumisano Municipal Hospital, Izumisano, Osaka, Japan

Submitted 10 October 2007 ; accepted in final form 15 January 2008

Mesenchymal stem cells (MSCs), a subpopulation of adult somatic stem cells, are an attractive stem cell source in regenerative medicine because of their multipotentiality. We examined the effects of MSC transplantation on gastric ulcer healing. Putative MSCs, isolated from bone marrow aspirates of male rats by dish adherence and expanded in culture, were characterized by flow cytometry and reverse transcription-polymerase chain reaction. Gastric ulcers were induced by serosal application of acetic acid on the anterior wall of the stomach in female rats. Either MSCs (labeled with PKH67; 1x107 cells) or vehicle was injected into the gastric wall surrounding the ulcer. The healing process of the ulcer and the influence of anti-vascular endothelial growth factor (VEGF) antibody were examined. CD29-positive, CD90-positive, CD34-negative, and CD45-negative MSCs expressed mRNAs for VEGF and hepatocyte growth factor (HGF). The MSCs were transplantable to the gastric tissue surrounding the ulcer, where a majority of the engrafted cells were positive for vimentin. The transplantation significantly accelerated gastric ulcer healing compared with controls. The engrafted MSCs also expressed VEGF and HGF. Administration of anti-VEGF neutralizing antibody dose dependently reduced the MSC-induced promotion of ulcer healing. In conclusion, MSC transplantation accelerated gastric ulcer healing, possibly through the induction of angiogenesis in the gastric mucosa via the secretion of VEGF. The beneficial effects of MSCs might be mediated not only by their differentiation into gastric interstitial cells, but also by their ability to supply angiogenic factors.

bone marrow; mesenchymal stromal cells


Address for reprint requests and other correspondence: S. Tsuji, Dept. of Gastroenterology and Hepatology, Osaka Univ. Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan (e-mail: stsuji{at}gh.med.osaka-u.ac.jp)






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