Toll-like receptor 3 pre-conditioning increases the therapeutic efficacy of umbilical cord mesenchymal stromal cells in a dextran sulfate sodium-induced colitis model

Patricia Fuenzalida, Mónica Kurte, Catalina Fernández-O'ryan, Cristina Ibañez, Melanie Gauthier-Abeliuk, Ana María Vega-Letter, Paz Gonzalez, Carlos Irarrázabal, Nataly Quezada, Fernando Figueroa, Flavio Carrión

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Background aims: Immunomodulatory properties of human umbilical cord-derived mesenchymal stromal cells (UCMSCs) can be differentially modulated by toll-like receptors (TLR) agonists. Here, the therapeutic efficacy of short TLR3 and TLR4 pre-conditioning of UCMSCs was evaluated in a dextran sulfate sodium (DSS)-induced colitis in mice. The novelty of this study is that although modulation of human MSCs activity by TLRs is not a new concept, this is the first time that short TLR pre-conditioning has been carried out in a murine inflammatory model of acute colitis. Methods: C57BL/6 mice were exposed to 2.5% dextran sulfate sodium (DSS) in drinking water ad libitum for 7 days. At days 1 and 3, mice were injected intraperitoneally with 1 × 106 UCMSCs untreated or TLR3 and TLR4 pre-conditioned UCMSCs. UCMSCs were pre-conditioned with poly(I:C) for TLR3 and LPS for TLR4 for 1 h at 37°C and 5% CO2. We evaluated clinical signs of disease and body weights daily. At the end of the experiment, colon length and histological changes were assessed. Results: poly(I:C) pre-conditioned UCMSCs significantly ameliorated the clinical and histopathological severity of DSS-induced colitis compared with UCMSCs or LPS pre-conditioned UCMSCs. In contrast, infusion of LPS pre-conditioned UCMSCs significantly increased clinical signs of disease, colon shortening and histological disease index in DSS-induced colitis. Conclusions: These results show that short in vitro TLR3 pre-conditioning with poly(I:C) enhances the therapeutic efficacy of UCMSCs, which is a major breakthrough for developing improved treatments to patients with inflammatory bowel disease.
Original languageAmerican English
Pages (from-to)630-641
Number of pages12
JournalCytotherapy
Volume18
Issue number5
DOIs
StatePublished - 1 May 2016

Keywords

  • Cell therapy
  • Dextran sulfate sodium-induced colitis
  • Immunosuppression
  • Inflammatory bowel disease
  • Toll-like receptors
  • Umbilical cord-derived mesenchymal stromal cells

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