TY - JOUR
T1 - Toll-like receptor 3 pre-conditioning increases the therapeutic efficacy of umbilical cord mesenchymal stromal cells in a dextran sulfate sodium-induced colitis model
AU - Fuenzalida, Patricia
AU - Kurte, Mónica
AU - Fernández-O'ryan, Catalina
AU - Ibañez, Cristina
AU - Gauthier-Abeliuk, Melanie
AU - Vega-Letter, Ana María
AU - Gonzalez, Paz
AU - Irarrázabal, Carlos
AU - Quezada, Nataly
AU - Figueroa, Fernando
AU - Carrión, Flavio
N1 - Funding Information:
This work was supported by a grant from Fondo Nacional de Desarrollo Científico y Tecnológico (Fondecyt 1130444 ), Santiago Chile.
Publisher Copyright:
© 2016 International Society for Cellular Therapy.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
KW - Cell therapy
KW - Dextran sulfate sodium-induced colitis
KW - Immunosuppression
KW - Inflammatory bowel disease
KW - Toll-like receptors
KW - Umbilical cord-derived mesenchymal stromal cells
UR - http://www.scopus.com/inward/record.url?scp=84962113337&partnerID=8YFLogxK
U2 - 10.1016/j.jcyt.2016.02.002
DO - 10.1016/j.jcyt.2016.02.002
M3 - Article
C2 - 27059200
AN - SCOPUS:84962113337
SN - 1465-3249
VL - 18
SP - 630
EP - 641
JO - Cytotherapy
JF - Cytotherapy
IS - 5
ER -