title: Combined effect of bone marrow derived mesenchymal stem cells and nitric oxide inducer on injured gastric mucosa in a rat model.
abstract: OBJECTIVE
  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 (106cells) by intravenous injection. l-Arginine was given 300mg/kg body weight intraperitoneally. 24h and 7days after BMMSCs and NO inducer injection, VEGF, PGE, TNF-α were assessed by ELISA. Gene expression of HGF, caspase-3, eNOS and BAX/Bcl-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 24h and 7days 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-α levels in the gastric ulcer group receiving MSCs, the gastric ulcer group receiving NO and the gastric ulcer group receiving both MSCs andNO compared to the gastric ulcer group after both 24h and 7days. 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.
authors.forename: Laila
authors.initials: L
authors.lastname: Rashed
authors.affiliation: Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Cairo University, Cairo 11562, Egypt. Electronic address: drdoaagharib@kasralainy.edu.eg.
authors.forename: Doaa Mostafa
authors.initials: DM
authors.lastname: Gharib
authors.affiliation: Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.
authors.forename: Rania Elsayed
authors.initials: RE
authors.lastname: Hussein
authors.affiliation: Department of Physiology, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.
authors.forename: Ola
authors.initials: O
authors.lastname: Tork
authors.affiliation: Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.
authors.forename: Azza
authors.initials: A
authors.lastname: Abusree
mesh_terms: D000818:Animals; D001120:Arginine / Q000008:administration & dosage; D001854:Bone Marrow Cells / Q000166:cytology; D005753:Gastric Mucosa / Q000187:drug effects / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D013276:Stomach Ulcer / Q000473:pathology / Q000628:therapy*; D014945:Wound Healing
chemical_list: D009569:Nitric Oxide; D001120:Arginine
keywords: Mesenchymal stem cells; NO; Refractory peptic ulcer; Stem cells therapy; e-NOS