Abstract
Aim: To study the effect of intravenous injection of bone marrow mesenchymal stem cells (BMMSCs), alone and combined with NO inducer in gastric ulcer healing in a rat model.
Methods: Rats were divided into controls, gastric ulcer, gastric ulcer receiving mesenchymal stem cells (MSCs), gastric ulcer receiving NO inducer (L-Arginine), gastric ulcer receiving MSCs plus NO inducer (L-Arginine) groups. MSCs were given in a dose of (10(6)cells) by intravenous injection. L-Arginine was given 300 mg/kg body weight intraperitoneally. 24 h and 7 days after BMMSCs and NO inducer injection, VEGF, PGE, TNF-alpha were assessed by ELISA. Gene expression of HGF, caspase-3, eNOS and BAX/Bc1-2 in gastric tissues were studied by real time PCR. Histopathology staining of gastric tissues was performed.
Results: Injection of MSCs or NO inducer or both to the gastric ulcer group significantly decreased caspase-3 and BAX genes expression (apoptotic factors) and increased Bcl-2 gene expression (anti-apoptotic factor) compared to that of the gastric ulcer group after both 24 h and 7 days with more significant results in the gastric group received both MSCs and NO inducer. HGF gene expression was significantly increased in the groups injected with MSCs or NO inducer or both compared with the corresponding gastric ulcer group (p < 0.05, p < 0.05 & p < 0.001 respectively). There was a significant decrease in the mean PGE2 and TNF-alpha levels in the gastric ulcer group receiving MSCs, the gastric ulcer group receiving NO and the gastric ulcer group receiving both MSCs and NO compared to the gastric ulcer group after both 24 h and 7 days. Histopathological examination of gastric tissue of groups that received stem cells or NO alone, showed mucosal regenerative changes with increased thickness together with reduced inflammatory cellular infiltrate in the submucosa and decreased congestion. There was complete restoration in gastric mucosa in the group that received both stem cells and NO.
Conclusion: Administration of MSCs, NO, or MSCs plus NO may exert a therapeutic effect on the mucosal lesion in gastric ulcer through their anti-inflammatory, angiogenic and antiapoptotic actions. (C) 2016 Elsevier Ltd. All rights reserved.