title: Umbilical cord mesenchymal stem cells modulate dextran sulfate sodium induced acute colitis in immunodeficient mice.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Gastroenterology/Multivisceral Transplant Unit, University Hospital Padova, Via Giustiniani 2, Padova, 35128, Italy. antara.banerjee27@gmail.com.
authors.forename: Antara
authors.initials: A
authors.lastname: Banerjee
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Gastroenterology/Multivisceral Transplant Unit, University Hospital Padova, Via Giustiniani 2, Padova, 35128, Italy. debora.bizzaro@gmail.com.
authors.forename: Debora
authors.initials: D
authors.lastname: Bizzaro
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Gastroenterology/Multivisceral Transplant Unit, University Hospital Padova, Via Giustiniani 2, Padova, 35128, Italy. burra@unipd.it.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Burra
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131, Padova, Italy. rosa.diliddo@unipd.it.
authors.forename: Rosa
authors.initials: R
authors.lastname: Di Liddo
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Gastroenterology/Multivisceral Transplant Unit, University Hospital Padova, Via Giustiniani 2, Padova, 35128, Italy. antara.banerjee27@gmail.com.
authors.forename: Surajit
authors.initials: S
authors.lastname: Pathak
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Gastroenterology/Multivisceral Transplant Unit, University Hospital Padova, Via Giustiniani 2, Padova, 35128, Italy. diletta.arcidiacono@unipd.it.|Venetian Institute of Molecular Medicine (VIMM), Via Orus, 2 35129, Padova, Italy. diletta.arcidiacono@unipd.it.
authors.forename: Diletta
authors.initials: D
authors.lastname: Arcidiacono
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Gastroenterology/Multivisceral Transplant Unit, University Hospital Padova, Via Giustiniani 2, Padova, 35128, Italy. cappon.andrea@gmail.com.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cappon
authors.affiliation: Obstetrics and Gynecology Unit, Cittadella Hospital, via Casa di ricovero, 40 35013 Cittadella, Padova, Italy. patriziobo@alice.it.
authors.forename: Patrizio
authors.initials: P
authors.lastname: Bo
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131, Padova, Italy. mariateresa.conconi@unipd.it.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Conconi
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Gastroenterology/Multivisceral Transplant Unit, University Hospital Padova, Via Giustiniani 2, Padova, 35128, Italy. marikacrescenzi@hotmail.com.
authors.forename: Marika
authors.initials: M
authors.lastname: Crescenzi
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Gastroenterology/Multivisceral Transplant Unit, University Hospital Padova, Via Giustiniani 2, Padova, 35128, Italy. maria.pinna84@gmail.com.
authors.forename: Claudia Maria Assunta
authors.initials: CM
authors.lastname: Pinna
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131, Padova, Italy. pierpaolo.parnigotto@unipd.it.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Parnigotto
authors.affiliation: Centre for Tumour Biology, Barts Cancer Institute, Charterhouse Square, London, EC1M 6BQ, UK. m.alison@qmul.ac.uk.
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Alison
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Gastroenterology/Multivisceral Transplant Unit, University Hospital Padova, Via Giustiniani 2, Padova, 35128, Italy. gc.sturniolo@unipd.it.
authors.forename: Giacomo Carlo
authors.initials: GC
authors.lastname: Sturniolo
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Gastroenterology/Multivisceral Transplant Unit, University Hospital Padova, Via Giustiniani 2, Padova, 35128, Italy. dinca@unipd.it.
authors.forename: Renata
authors.initials: R
authors.lastname: D'Incà
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Gastroenterology/Multivisceral Transplant Unit, University Hospital Padova, Via Giustiniani 2, Padova, 35128, Italy. francescopaolo.russo@unipd.it.
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Russo
mesh_terms: D000208:Acute Disease; D000818:Animals; D001835:Body Weight; D002374:Catalase / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D009195:Peroxidase / Q000378:metabolism; D012720:Severity of Illness Index; D014183:Transplantation, Heterologous; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D016264:Dextran Sulfate; D002374:Catalase; D009195:Peroxidase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9