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Umbilical cord mesenchymal stem cells modulate dextran sulphate sodium induced acute colitis in immunodeficient mice

Authors :
Maria Teresa Conconi
Debora Bizzaro
Claudia Maria Assunta Pinna
Patrizia Burra
Rosa Di Liddo
P. Bo
Antara Banerjee
Giacomo Carlo Sturniolo
Malcolm R. Alison
Marika Crescenzi
Francesco Paolo Russo
Diletta Arcidiacono
Surajit Pathak
Andrea Cappon
Pier Paolo Parnigotto
Renata D'Incà
Source :
Stem Cell Research & Therapy
Publication Year :
2015

Abstract

Introduction Inflammatory bowel diseases (IBD) are complex multi-factorial diseases with increasing incidence worldwide but their treatment is far from satisfactory. Unconventional strategies have consequently been investigated, proposing the use of cells as an effective alternative approach to IBD. In the present study we examined the protective potential of exogenously administered human umbilical cord derived mesenchymal stem cells (UCMSCs) against Dextran Sulfate Sodium (DSS) induced acute colitis in immunodeficient NOD.CB17-Prkdcscid/J mice with particular attention to endoplasmic reticulum (ER) stress. Methods UCMSCs were injected in NOD.CB17-Prkdcscid/J via the tail vein at day 1 and 4 after DSS administration. To verify attenuation of DSS induced damage by UCMSCs, Disease Activity Index (DAI) and body weight changes was monitored daily. Moreover, colon length, histological changes, myeloperoxidase and catalase activities, metalloproteinase (MMP) 2 and 9 expression and endoplasmic reticulum (ER) stress related proteins were evaluated on day 7. Results UCMSCs administration to immunodeficient NOD.CB17-Prkdcscid/J mice after DSS damage significantly reduced DAI (1.45 ± 0.16 vs 2.08 ± 0.18, p 3-fold), which were significantly reduced in mice receiving UCMSCs. Moreover, positive modulation in ER stress related proteins was observed after UCMSCs administration. Conclusions Our results demonstrated that UCMSCs are able to prevent DSS-induced colitis in immunodeficient mice. Using these mice we demonstrated that our UCMSCs have a direct preventive effect other than the T-cell immunomodulatory properties which are already known. Moreover we demonstrated a key function of MMPs and ER stress in the establishment of colitis suggesting them to be potential therapeutic targets in IBD treatment.

Details

Language :
English
Database :
OpenAIRE
Journal :
Stem Cell Research & Therapy
Accession number :
edsair.doi.dedup.....28f68122c12801abf4f6401dd36cb06a