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

Antara Banerjee, Debora Bizzaro, Patrizia Burra, Rosa Di Liddo, Surajit Pathak, Diletta Arcidiacono, Andrea Cappon, Patrizio Bo, Maria Teresa Conconi, Marika Crescenzi, Claudia Maria Assunta Pinna, Pier Paolo Parnigotto, Malcolm R. Alison, Giacomo Carlo Sturniolo, Renata D'Incà, Francesco Paolo Russo

Research output: Contribution to journalArticlepeer-review

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-Prkdc scid/J mice with particular attention to endoplasmic reticulum (ER) stress. Methods: UCMSCs were injected in NOD.CB17-Prkdc scid/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-Prkdc scid/J mice after DSS damage significantly reduced DAI (1.45 ± 0.16 vs 2.08 ± 0.18, p <0.05), attenuating the presence of bloody stools, weight loss, colon shortening (8.95 ± 0.33 cm vs 6.8 ± 0.20 cm, p <0.01) and histological score (1.97 ± 0.13 vs 3.27 ± 0.13, p <0.001). Decrease in neutrophil infiltration was evident from lower MPO levels (78.2 ± 9.7 vs 168.9 ± 18.2 U/g, p <0.01). DSS treatment enhanced MMP2 and MMP9 activities (>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.

Original languageEnglish
Article number79
JournalStem Cell Research and Therapy
Volume6
Issue number1
DOIs
Publication statusPublished - Apr 16 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Molecular Medicine
  • Cell Biology
  • Medicine (miscellaneous)

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