Submitted on October 10, 2007
Accepted on January 15, 2008
Topical Transplantation of Mesenchymal Stem Cells Accelerates Gastric Ulcer Healing in Rats
Yujiro Hayashi1, Shingo Tsuji2*, Masahiko Tsujii2, Tsutomu Nishida2, Shuji Ishii2, Hideki Iijima2, Toru Nakamura1, Hiroshi Eguchi1, Eiji Miyoshi1, Norio Hayashi2, and Sunao Kawano3
1 Department of Clinical Laboratory Science, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan
2 Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan
3 Izumisano Muncipal Hospital, Japan; Department of Clinical Laboratory Science, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan
* To whom correspondence should be addressed. E-mail: stsuji{at}gh.med.osaka-u.ac.jp.
Mesenchymal stem cells (MSCs), a subpopulation of adult somatic stem cells, are an attractive stem cell source in regenerative medicine due to 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. The MSCs, labeled with PKH67 (1x107 cells), or vehicle were 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 as 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. Conclusions: 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.
