title: Effects of human amnion-derived mesenchymal stromal cell transplantation in rats with radiation proctitis.
abstract: OBJECTIVE
  Mesenchymal stromal cells (MSCs) have been reported to be a promising cell source in cell therapy, and large amounts of MSCs can easily be isolated from human amnion. Therapeutic irradiation for intra-pelvic cancer often causes radiation proctitis; however, there is currently no effective treatment. We therefore investigated the effect of transplantation of human amnion-derived MSCs (AMSCs) in rats with radiation proctitis.
  
  
  METHODS
  Amnion was obtained at cesarean delivery, and AMSCs were isolated and expanded. Sprague-Dawley rats were γ-irradiated (5 Gy/d) at the rectum for 5 days. On day 5, AMSCs (1 × 10(6) cells) were intravenously transplanted. Rats were killed on day 8. Histological analyses were performed, and messenger RNA expression of inflammatory mediators was measured. In vitro, after γ-irradiation of rat intestinal epithelial cells (IEC-6), the cells were cultured with AMSC-conditioned medium (CM). The effect of AMSC-CM was evaluated by measurement of caspase-3/7 activity, p53 transcription activity and quantitative reverse-transcription-polymerase chain reaction for p53-target genes.
  
  
  RESULTS
  Histological examination demonstrated that epithelial injury and infiltration of inflammatory cells in the rectum were significantly suppressed by transplantation of AMSCs. In vitro, the cell injury in IEC-6 cells induced by γ-irradiation was inhibited by AMSC-CM, which also inhibited the upregulation of p53 transcription activity, caspase-3/7 activity and p21 expression.
  
  
  CONCLUSIONS
  Transplantation of AMSCs improved radiation proctitis, possibly through inhibition of cell injury and inflammatory reactions. AMSC transplantation should be considered as a new treatment for radiation proctitis.
authors.affiliation: Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Ono
authors.affiliation: Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. Electronic address: sonishi@pop.med.hokudai.ac.jp.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ohnishi
authors.affiliation: Laboratory of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Minori
authors.initials: M
authors.lastname: Honda
authors.affiliation: Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan; Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Marin
authors.initials: M
authors.lastname: Ishikawa
authors.affiliation: Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Hosono
authors.affiliation: Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Reizo
authors.initials: R
authors.lastname: Onishi
authors.affiliation: Laboratory of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Laboratory of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeda
authors.affiliation: Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
mesh_terms: D000650:Amnion / Q000166:cytology*; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects; D015870:Gene Expression; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology; D011247:Pregnancy; D011349:Proctitis / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D017077:Culture Media, Conditioned; D053148:Caspase 3
keywords: amnion; cell injury; mesenchymal stromal cells; radiation proctitis