Targeting of deciduous tooth pulp stem cell-derived extracellular vesicles on telomerase-mediated stem cell niche and immune regulation in systemic lupus erythematosus

Soichiro Sonoda, Sara Murata, Hiroki Kato, Fouad Zakaria, Yukari Kyumoto-Nakamura, Norihisa Uehara, Haruyoshi Yamaza, Toshio Kukita, Takayoshi Yamaza

研究成果: Contribution to journalArticle査読

抄録

Systemic transplantation of stem cells from human exfoliated deciduous teeth (SHED) is used to treat systemic lupus erythematosus (SLE)-like disorders in MRL/lpr mice. However, the mechanisms underlying the SHED-based therapy remain unclear. In this study, we hypothesized that trophic factors within SHED-releasing extracellular vesicles (SHED-EVs) ameliorate the SLE-like phenotypes in MRL/lpr mice. SHED-EVs were isolated from the culture supernatant of SHED. SHED-EVs were treated with or without RNase and systemically administered to MRL/lpr mice. Subsequently, recipient bone marrow mesenchymal stem cells (BMMSCs) isolated from SHED-EV-administered MRL/lpr mice were examined for the in vitro and in vivo activity of hematopoietic niche formation and immunoregulation. Furthermore, the recipient BMMSCs were secondarily transplanted into MRL/lpr mice. The systemic SHED-EV infusion ameliorated the SLE-like phenotypes in MRL/lpr mice and improved the functions of recipient BMMSCs by rescuing Tert mRNA-associated telomerase activity, hematopoietic niche formation, and immunoregulation. The secondary transplantation of recipient BMMSCs recovered the immune condition and renal functions of MRL/lpr mice. The RNase treatment depleted RNAs, such as microRNAs, within SHED-EVs, and the RNA-depleted SHED-EVs attenuated the benefits of SHED-EVs in MRL/lpr mice. Collectively, our findings suggest that SHED-secreted RNAs, such as microRNAs, play a crucial role in treating SLE by targeting the telomerase activity of recipient BMMSCs.

本文言語英語
ページ(範囲)3053-3063
ページ数11
ジャーナルJournal of Immunology
206
12
DOI
出版ステータス出版済み - 6 15 2021

All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学

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