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; 1x10(7) 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.