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Abstract: TH-OR039

Hepatocyte Growth Factor-Producing Mesothelial Cell Sheets Reduce Apoptosis of Renal Tubular Epithelial Cells in Ischemia-Reperfusion Injury

Session Information

  • Bioengineering
    November 07, 2019 | Location: 146 A/B, Walter E. Washington Convention Center
    Abstract Time: 06:06 PM - 06:18 PM

Category: Bioengineering

  • 300 Bioengineering

Authors

  • Miyabe, Yoei, Tokyo Women's Medical University, Tokyo, Japan
  • Sekiya, Sachiko, Institute of Advanced Biomedical Engineering and Science, Tokyo, Japan
  • Sugiura, Naoko, Tokyo Women's Medical University, Tokyo, Japan
  • Karasawa, Kazunori, Tokyo Women's Medical University, Tokyo, Japan
  • Nitta, Kosaku, Tokyo Women's Medical University, Tokyo, Japan
Background

Ischemia-reperfusion injury (IRI) is a model of acute kidney injury and chronic kidney disease which are clinically important problems to be solved. We have recently reported that renal subcapsular transplantation of hepatocyte growth factor (HGF)-producing cell sheets improved renal IRI in rats from acute to chronic phase. However, the mechanism is not well understood. Therefore, we assessed the apoptosis of the renal tubular epithelial cells after IRI with or without transplantation of the HGF-producing cell sheets.

Methods

HGF-transgenic human mesothelial cells (HGF-tg MC sheet) were cultured in temperature-responsive dishes for 4 days to prepare cell sheets. At day 7 after right nephrectomyon a nude rat, two cell sheets were transplanted under the left renal capsule, and the left renal pedicle was clamped for 60 min.Reperfusion was performed after the ischemia, and the left kidney was harvestedat day 2, 14, and 28 after IRI. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and caspase-3 staining were performed to evaluate apoptosis with paraffin-embedded sections of the kidney. HGF-tg MC sheet group was compared to other groups; a sham operation without IRI or treatment (Sham); IRI with no treatment (NT); IRI with intravenous administration of recombinant human HGF protein (IV HGF); or IRI with transplantation of non-transgenic MC sheets under the renal capsule (MC sheet).

Results

The number of caspase-3-positive cells was highest in the Sham group, lowest in the NT group, and somewhat higher in the other groups. WithTUNEL staining, positive cells were significantly suppressed in the HGF-tg MC sheet group and MC sheet group, compared to NT group and IV HGF group.

Conclusion

Transplantation of HGF-producing cell sheets under the renal capsule may reduce apoptosis in renal tubular epithelial cells. These results suggested that the suppression of apoptosis is one of the mechanisms to improve IRI by HGF-producing cell sheets.

Funding

  • Government Support - Non-U.S.