論文

査読有り 国際誌
2022年7月16日

Implantation of dedifferentiated fat cells ameliorated antineutrophil cytoplasmic antibody glomerulonephritis by immunosuppression and increases in tumor necrosis factor-stimulated gene-6.

Stem cell research & therapy
  • Kei Utsunomiya
  • ,
  • Takashi Maruyama
  • ,
  • Satoshi Shimizu
  • ,
  • Taro Matsumoto
  • ,
  • Morito Endo
  • ,
  • Hiroki Kobayashi
  • ,
  • Koichiro Kano
  • ,
  • Masanori Abe
  • ,
  • Noboru Fukuda

13
1
開始ページ
319
終了ページ
319
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1186/s13287-022-03014-8

INTRODUCTION: The implantation of dedifferentiated fat (DFAT) cells has been shown to exert immunosuppressive effects. To develop DFAT cell therapy for antineutrophil cytoplasmic antibody (ANCA) glomerulonephritis, the effects of the implantation of DFAT cells on ANCA glomerulonephritis were investigated in mice. METHODS: PKH26-labeled DFAT cells (105) were infused through the posterior orbital venous plexus to investigate delivery of DFAT cells in ICR mice. DFAT cells (105) were also implanted in SCG mice as a model for ANCA glomerulonephritis. Expression of tumor necrosis factor-stimulated gene-6 (TSG-6) mRNA and protein in kidney was evaluated, and the expression of microRNAs associated with TSG-6 in plasma, lung and kidney was analyzed. Expressions of CD44, prostaglandin (PG) E2, interleukin (IL)-10, IL-1β, tumor necrosis factor (TNF)-α mRNAs, C-C motif chemokine ligand 17 (CCL-17) and monocyte chemoattractant protein (MCP)-1 proteins were measured in kidney from SCG mice implanted with DFAT cells. RESULTS: After their intravenous infusion, almost all DFAT cells were trapped in the lung and not delivered into the kidney. Implantation of DFAT cells in SCG mice suppressed glomerular crescent formation, decreased urinary protein excretions and increased expression of TSG-6 mRNA, protein and immunostaining in kidney from these mice. Increased expression of microRNA 23b-3p in plasma, kidney and lung; decreased expression of CD44 mRNA; and increased expression of PGE2 and IL-10 mRNAs were also observed in kidney from these mice. Implantation of DFAT cells also decreased the expression of TNF-α and MCP-1 proteins and increased that of CCL-17 protein in kidney from the SCG mice. Survival rates were higher in SCG mice implanted with DFAT cells than in SCG mice without implantation. CONCLUSION: Mechanisms underlying the effects of improvement of ANCA glomerulonephritis are associated with immunosuppressive effects by TSG-6 and the transition of M1-M2 macrophages, suggesting that implantation of DFAT cells may become a cell therapy for ANCA glomerulonephritis.

リンク情報
DOI
https://doi.org/10.1186/s13287-022-03014-8
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/35842674
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288725
ID情報
  • DOI : 10.1186/s13287-022-03014-8
  • PubMed ID : 35842674
  • PubMed Central 記事ID : PMC9288725

エクスポート
BibTeX RIS