Linked Life Data

19291714

Source:http://linkedlifedata.com/resource/pubmed/id/19291714

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-6-11
pubmed:abstractText
The cellular origin, in vivo function and fate of donor bone marrow-derived cells residing in the recipient intestinal epithelial cells, pericryptal myofibroblasts or endothelial cells remain obscure. Although 'immunoprivileged' mesenchymal stem cells (MSCs) are prime candidates for cell- and gene-based therapy, their precise role in colitis remains largely undetermined. Using a dextran sulphate sodium (DSS) colitis with busulphan (BU)-induced hypoplastic marrow model, we examined the therapeutic effects of MSC transplantation, focusing on the role of MSCs as both cell providers and immunomodulators. Donor-derived MSCs were detected by eGFP immunofluorescence and fluorescence in situ hybridization for Y-chromosome (Y-FISH) analysis. Western blot analysis of apical-most tight junction proteins was performed with antibodies against claudin-2, -7, -8, -12, -13, -15 and ZO-1. Cytokine and cell cycle profiles were analysed by semi-quantitative RT-PCR and flow cytometry. Susceptibility to DSS colitis was significantly increased by co-existing BU-induced bone marrow hypoplasia and this increase was significantly reduced by enhancing epithelial engraftment of MSCs, an effect depending on restoring epithelial barrier integrity rather than inhibiting host immune responses. We provide evidence that implicates MSCs in maintaining epithelial barrier function by reassembling apical-most tight junction proteins, claudins. The therapeutic efficacy of extrinsic MSCs depends on enhancing epithelial engraftment in damaged crypts by busulphan conditioning. Such a role for the MSC-derived intestinal cells in colitis therapy merits further examination and may offer a promising new treatment for inflammatory bowel disease (IBD).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1096-9896
pubmed:author
pubmed:copyrightInfo
2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
pubmed:issnType
Electronic
pubmed:volume
218
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
350-9
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Enhancing epithelial engraftment of rat mesenchymal stem cells restores epithelial barrier integrity.
pubmed:affiliation
First Department of Internal Medicine, Sapporo Medical University, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Evaluation Studies