Topical transplantation of mesenchymal stem cells accelerates gastric ulcer healing in rats.
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.
Hayashi
Yujiro
Y
Department of Clinical Laboratory Science, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
Tsuji
Shingo
S
Tsujii
Masahiko
M
Nishida
Tsutomu
T
Ishii
Shuji
S
Iijima
Hideki
H
Nakamura
Toru
T
Eguchi
Hiroshi
H
Miyoshi
Eiji
E
Hayashi
Norio
N
Kawano
Sunao
S
D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013276:Stomach Ulcer / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor