(Gut 1999;45:856-863)

Background and AimsMesenchymal stromal cells (MSCs) were shown to have immunomodulatory activity and have been applied for treating immune-mediated disorders. We compared the homing and therapeutic action of cryopreserved subcutaneous adipose tissue (AT-MSCs) and bone marrow-derived mesenchymal stromal cells (BM-MSCs) in rats with trinitrobenzene sulfonic acid (TNBS)–induced colitis.MethodsAfter colonoscopic detection of inflammation AT-MSCs or BM-MSCs were injected intraperitoneally. Colonoscopic and histologic scores were obtained. Density of collagen fibres and apoptotic rates were evaluated. Cytokine levels were measured in supernatants of colon explants. For cell migration studies MSCs and skin fibroblasts were labelled with Tc-99m or CM-DiI and injected intraperitonealy or intravenously.ResultsIntraperitoneal injection of AT-MSCs or BM-MSCs reduced the endoscopic and histopathologic severity of colitis, the collagen deposition, and the epithelial apoptosis. Levels of TNF-α and interleukin-1β decreased, while VEGF and TGF-β did not change following cell-therapy. Scintigraphy showed that MSCs migrated towards the inflamed colon and the uptake increased from 0.5 to 24 h. Tc-99m-MSCs injected intravenously distributed into various organs, but not the colon. Cm-DiI-positive MSCs were detected throughout the colon wall 72 h after inoculation, predominantly in the submucosa and muscular layer of inflamed areas.ConclusionsIntraperitoneally injected cryopreserved MSCs home to and engraft into the inflamed colon and ameliorate TNBS-colitis.

Increased expression of FasL in IBD colonic LP not parallelled by Fas on T-cells and macrophages may indicate a reduced susceptibility to the Fas/FasL-mediated apoptosis of lymphoid cells. Expression of perforin is correlated to the tissue damage, and may represent the enhancement of a distinct cytotoxic pathway in UC.

SUMMARYT cell subsets in the gut mucosa are disliiicl populations and their imbalance in HIV has specilic implications in infection. Alterations in T cell subsets in duodenal biopsies vvere investigated in 17 asymptomatic HIV patients, 24 AIDS patienis and 10 controls wilh non-ulcer dyspepsia. Immunohistochemislry and immunofluorescence using MoAbs to CD3, CD4, CDS, CD68, CD45RA, CD45RO and gp 120 were performed on frozen sections. In the lamina propria, there was a significant depletion of CD4'^ cells at all stages of HIV, bul the density of CDS lamina propria cells was increased. Iniraepithelial lymphocytes were decreased in AIDS patients. There was a signilieunl correlation between cellular density and mucosal CD3 ' lymphocytes, and between mucosal CD3' and CDS' lymphocytes. Allhotigh mucosal CD4,CD45RO* 'memory" cells were decreased, CD8,CD45RO^ 'memory cells were increased. MucosatCD4' lymphocyte depletion occurred early in HIV, and thus their role in mueosal proleciion against opportunistic infeetion should be revised. Mucosal CD8' lymphocytes initially increased, but decreased when CD4 blood counts were depicted, perhaps contributing to loss ofhost protection against infection. Intraepitheiial lymphocyte depletion may also eontHbute lo opportunisiic infeciion.