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Umbilical cord mesenchymal stem cells modulate dextran sulphate sodium induced acute colitis in immunodeficient mice
- 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.
- Subjects :
- Male
Colon
Transplantation, Heterologous
Medicine (miscellaneous)
Mesenchymal Stem Cell Transplantation
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Umbilical cord
Severity of Illness Index
Umbilical Cord
Mice
Mice, Inbred NOD
Medicine
Animals
Humans
Colitis
Acute colitis
Peroxidase
biology
business.industry
Research
Mesenchymal stem cell
Body Weight
Dextran Sulfate
Mesenchymal Stem Cells
Cell Biology
medicine.disease
Catalase
Transplantation
Disease Models, Animal
medicine.anatomical_structure
Matrix Metalloproteinase 9
Myeloperoxidase
Immunology
Acute Disease
Unfolded protein response
biology.protein
Cancer research
Molecular Medicine
Matrix Metalloproteinase 2
Stem cell
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Stem Cell Research & Therapy
- Accession number :
- edsair.doi.dedup.....28f68122c12801abf4f6401dd36cb06a