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Effects of human amnion-derived mesenchymal stromal cell transplantation in rats with radiation proctitis

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Title: Effects of human amnion-derived mesenchymal stromal cell transplantation in rats with radiation proctitis
Authors: Ono, Masayoshi Browse this author
Ohnishi, Shunsuke Browse this author →KAKEN DB
Honda, Minori Browse this author
Ishikawa, Marin Browse this author
Hosono, Hidetaka Browse this author
Onishi, Reizo Browse this author
Nakagawa, Koji Browse this author →KAKEN DB
Takeda, Hiroshi Browse this author →KAKEN DB
Sakamoto, Naoya Browse this author →KAKEN DB
Keywords: amnion
cell injury
mesenchymal stromal cells
radiation proctitis
Issue Date: Nov-2015
Publisher: Elsevier
Journal Title: Cytotherapy
Volume: 17
Issue: 11
Start Page: 1545
End Page: 1559
Publisher DOI: 10.1016/j.jcyt.2015.07.003
PMID: 26256683
Abstract: Background aims. 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 gamma-irradiated (5 Gy/d) at the rectum for 5 days. On day 5, AMSCs (1 x 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 gamma-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 gamma-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.
Rights: © 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 大西 俊介

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