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

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 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: Masayoshi Ono, Shunsuke Ohnishi, Minori Honda, Marin Ishikawa, Hidetaka Hosono, Reizo Onishi, Koji Nakagawa, Hiroshi Takeda, Naoya Sakamoto
• Journal: Cytotherapy (Cytotherapy) Vol. 17 Issue 11 Pg. 1545-59 (Nov 2015) ISSN: 1477-2566 [Electronic] England
• PMID: 26256683 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Chemical References

• Culture Media, Conditioned
• Caspase 3

Topics

• Amnion (cytology)
• Animals
• Caspase 3 (metabolism)
• Cell- and Tissue-Based Therapy (methods)
• Cells, Cultured
• Culture Media, Conditioned (metabolism, pharmacology)
• Epithelial Cells (drug effects)
• Female
• Gamma Rays (adverse effects)
• Gene Expression
• Humans
• Male
• Mesenchymal Stem Cell Transplantation (methods)
• Mesenchymal Stem Cells (metabolism, physiology)
• Pregnancy
• Proctitis (etiology, pathology, therapy)
• Rats
• Rats, Sprague-Dawley