Mo2008 Ameliorative Potentials of Human Umbilical Cord Derived Mesenchymal Stem Cells in Dextran Sulphate Sodium Induced Acute Colitis in NOD.Cb17-Prkdcscid/J Mice

Abstract

Introduction: Recent evidences suggest therapeutic value of mesenchymal stem cells (MSCs) as anti-inflammatory and immunomodulatory agent against several autoimmune diseases. Although promising, stem cell based therapies for IBD still requires experimental validation. In the present study we sought to determine whether exogenous administration of human umbilical cord derived cells with phenotype consistent with MSCs (UC-MSCs) can reduce acute colonic damage induced by Dextran Sulphate Sodium (DSS) in immunodeficient NOD.CB17-Prkdcscid/Jmice.Methods: UC-MSCs isolatedwere evaluated by assessing CD73, CD90, CD166, CD105, CD29, CD44, HLA-DR and c-kit expression, by adipocyte, osteocyte differentiation and proliferation potential by cell cycle analysis and wound assay. UC-MSCs were injected in NOD.CB17-Prkdcscid/J mice via tail vein at day 1 and 4. Disease Activity Index, daily body weight changes and colon length, and histological changes evaluated on day 7. Myeloperoxidase, catalase activities, chromosome aberration, sperm head anomaly and metalloproteinase (MMP) 2, 9 expressions were assessed in mice to verify attenuation of DSS induced damage by UC-MSCs. Alteration of ER stress related proteins like BIP, PERK, PDI, CHOP were studied by western blotting. Results: UC-MSC differentiated in osteocytes/ adipocytes, highly expressed CD90, CD73, CD166, CD105 andCD29 typical ofmesenchymal stem cells. UC-MSCs were successfully engrafted in the colon as evident from immunohistochemical staining against anti human nuclei antibody. UC-MSCs administration significantly attenuated bloody stool, weight loss, colon shortening and accelerated healing of damaged mucosa. Decrease in cytotoxicity and genotoxicity was evident from lower MPO level (78.2±9.7 vs 168.9±18.2 U/g, p 3 fold) which were reduced in UC-MSC group. Positive modulation in BIP, PERK, PDI proteins was noticed after MSC administration. Conclusions: NOD.CB17-Prkdcscid/J mice were susceptible to acute DSS colitis, suggesting that T, B and NK cells are not required for the disease. The engrafted UC-MSCs successfully accelerated healing of DSS-induced damaged tissue by promoting tissue repair process by reducing the protease burden through reduced MMP expression in inflammed colon and positively modulating histological score supporting the use of MSCs as a novel therapeutic strategy for colonic injuries. Future works in this direction would hopefully resolve the minutes of this inspiring cell therapy in alleviation of human sufferings involving IBDs.