Factors associated with thiopurine non-adherence in patients with inflammatory bowel disease.

BACKGROUND: Medication non-adherence seems to be a particular problem in younger patients with inflammatory bowel disease (IBD) and has a negative impact on disease outcome. AIMS: To assess whether non-adherence, defined using thiopurine metabolite levels, is more common in young adults attending a transition clinic than adults with IBD and whether psychological co-morbidity is a contributing factor. We also determined the usefulness of the Modified Morisky 8-item Adherence Scale (MMAS-8) to detect non-adherence. METHODS: Seventy young adults [51% (36) male] and 74 [62% (46) male] adults were included. Psychological co-morbidity was assessed using the Hospital Anxiety Depression Scale (HADS) and self-reported adherence using the MMAS-8. RESULTS: Twelve percent (18/144) of the patients were non-adherent. Multivariate analysis [OR, (95% CI), P value] confirmed that being young adult [6.1 (1.7-22.5), 0.001], of lower socio-economic status [1.1 (1.0-1.1), <0.01] and reporting higher HADS-D scores [1.2 (1.0-1.4), 0.01] were associated with non-adherence. Receiver operator curve analysis of MMAS-8 scores gave an area under the curve (95% CI) of 0.85 (0.77-0.92), (P < 0.0001): using a cut-off of <6, the MMAS-8 score has a sensitivity of 94% and a specificity of 64% to predict thiopurine non-adherence. Non-adherence was associated with escalation in therapy, hospital admission and surgeries in the subsequent 6 months of follow up. CONCLUSIONS: Non-adherence to thiopurines is more common in young adults with inflammatory bowel disease, and is associated with lower socio-economic status and depression. The high negative predictive value of MMAS-8 scores <6 suggests that it could be a useful screen for thiopurine non-adherence.

Bone marrow transplantation ameliorates pathology in interleukin-10 knockout colitic mice.

The authors have previously reported the derivation of colonic subepithelial myofibroblasts (SEMFs) in both humans and mice from bone marrow (BM). In the pathogenesis of inflammatory bowel disease (IBD), such as Crohn's disease and ulcerative colitis, colonic SEMFs mediate several types of inflammatory response. In the present study, interleukin (IL)-10-/- mice were used as a model of IBD to investigate the involvement of BM-derived cells in the inflamed mucosa. Male whole BM [either C57/BL10 (wild type: WT) or IL-10-/- donor mice] was used to perform bone marrow transplantation (BMT) into both WT and IL-10-/- female mice. Tissue samples were evaluated by immunohistochemistry for alpha-smooth muscle actin expression and by in situ hybridization using a Y-chromosome-specific probe to track the donor-derived colonic SEMFs. The mucosal expression of mRNA for pro-inflammatory cytokines was analysed by reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, mRNA expression of matrix metalloproteinase (MMP)-7 and osteopontin in the inflamed mucosa was assessed using in situ hybridization. Body weights and histological scores showed that IL-10-/- mice that received WT BM had an improved course of colitis, decreased mucosal pro-inflammatory mRNA expression, and up to 30% of their SEMFs were of BM origin. Conversely, IL-10-/- mice receiving IL-10-/- BM progressed to extensive colitis, and Y probe analysis revealed that up to 45% of colonic SEMFs were of BM origin. WT mice receiving IL-10-/- or WT BM had no signs of colonic inflammation. The expression of MMP-7 and osteopontin was up-regulated in the inflamed mucosa. In conclusion, IL-10-/- mice displayed ameliorated disease activity after WT BMT, whilst colitis was not induced in WT mice by IL-10-/- BMT. The contribution of BM-derived cells to colonic SEMFs was significantly increased in the inflamed mucosa compared with non-inflamed mucosa.

Circulating mesenchymal stem cells.

Mesenchymal precursor cells (MPCs) are multipotent cells capable of differentiating into various mesenchymal tissues, such as bone, cartilage, fat, tendon and muscle. They are present within both mesenchymal tissues and the bone marrow (BM). If marrow-derived MPCs are to have a role in repair and fibrosis of mesenchymal tissues, transit of these cells through the peripheral blood is to be expected. Although there is evidence for the existence of MPCs within the peripheral blood, results are debated and are not always reproducible. Variations in the methods of cell purification, culture and characterisation may explain the inconsistent results obtained in different studies.

Recipes for adult stem cell plasticity: fusion cuisine or readymade?

A large body of evidence supports the idea that certain adult stem cells, particularly those of bone marrow origin, can engraft at alternative locations, particularly when the recipient organ is damaged. Under strong and positive selection pressure these cells will clonally expand/differentiate, making an important contribution to tissue replacement. Similarly, bone marrow derived cells can be amplified in vitro and differentiated into many types of tissue. Despite seemingly irrefutable evidence for stem cell plasticity, a veritable chorus of detractors has emerged, some doubting its very existence, motivated perhaps by more than a little self interest. The issues that have led to this situation include the inability to reproduce certain quite startling observations, and extrapolation from the behaviour of embryonic stem cells to suggest that adult bone marrow cells simply fuse with other cells and adopt their phenotype. Although these issues need resolving and, accepting that cell fusion does appear to allow reprogramming of haemopoietic cells in special circumstances, criticising this whole new field because some areas remain unclear is not good science.

The new stem cell biology: something for everyone.

The ability of multipotential adult stem cells to cross lineage boundaries (transdifferentiate) is currently causing heated debate in the scientific press. The proponents see adult stem cells as an attractive alternative to the use of embryonic stem cells in regenerative medicine (the treatment of diabetes, Parkinson's disease, etc). However, opponents have questioned the very existence of the process, claiming that cell fusion is responsible for the phenomenon. This review sets out to provide a critical evaluation of the current literature in the adult stem cell field.