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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)3053-3063
Number of pages11
JournalJournal of Immunology
Volume206
Issue number12
DOIs
Publication statusPublished - Jun 15 2021

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Targeting of deciduous tooth pulp stem cell-derived extracellular vesicles on telomerase-mediated stem cell niche and immune regulation in systemic lupus erythematosus'. Together they form a unique fingerprint.

Cite this