Mairi Brittan

The University of Edinburgh, Edinburgh, SCT, United Kingdom

Are you Mairi Brittan?

Claim your profile

Publications (44)283.56 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Innate immune responses to pulmonary resection may be critical in the pathogenesis of important postoperative pulmonary complications and potentially longer-term survival. We sought to compare innate immunity of patients undergoing major pulmonary resection for bronchogenic carcinoma via video-assisted thoracoscopic surgery (VATS) and thoracotomy. Bronchoalveolar lavage was conducted in the contralateral lung before staging bronchoscopy and mediastinoscopy and immediately after lung resection. Blood and exhaled nitric oxide were sampled preoperatively and at 6, 24, and 48 hours postoperatively. Forty patients were included (26 VATS and 14 thoracotomy). There was a lower systemic cytokine response from lung resection undertaken by VATS compared with thoracotomy [interleukin 6 (IL-6), analysis of variance (ANOVA) P = 0.026; IL-8, ANOVA P = 0.018; and IL-10, ANOVA P = 0.047]. The VATS patients had higher perioperative serum albumin levels (ANOVA P = 0.001). Lower levels of IL-10 were produced by lipopolysaccharide-stimulated blood monocytes from the VATS patients compared with the thoracotomy patients at 6 hours postoperatively (geometric mean ratio, 1.16; 95% confidence interval, 1.08-1.33; P = 0.011). No statistically significant differences in the neutrophil phagocytic capacity, overall leukocyte count, or differential leukocyte count were found between the surgical groups (ANOVA P > 0.05). No statistically significant differences in bronchoalveolar lavage fluid parameters were found. Exhaled nitric oxide levels fell postoperatively, which reached statistical significance at 48 hours (geometric mean ratio, 1.2; 95% confidence interval, 1.02-1.46; P = 0.029). There were no significant differences found between the surgical groups (ANOVA P = 0.331). Overall, a trend toward greater proinflammatory and anti-inflammatory responses is seen with lung resection performed via thoracotomy compared with VATS.
    Innovations Technology and Techniques in Cardiothoracic and Vascular Surgery 04/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We have previously reported the presence of novel subpopulations of pulmonary monocyte-like cells (PMLC) in the human lung; resident PMLC (rPMLC, HLA-DR+CD14++CD16+cells) and inducible PMLC (iPMLC, HLA-DR+CD14++CD16- cells). iPMLC are significantly increased in bronchoalveolar lavage (BAL) fluid following inhalation of lipopolysaccharide (LPS). We have carried out the first functional evaluation of PMLC subpopulations in the inflamed lung, following the isolation of these cells, and other lineages, from BAL fluid using novel and complex protocols. iPMLC, rPMLC, alveolar macrophages (AM), neutrophils, and regulatory T cells were quantified in BAL fluid of healthy subjects at 9 hours post-LPS inhalation (n = 15). Cell surface antigen expression by iPMLC, rPMLC and AM and the ability of each lineage to proliferate and to undergo phagocytosis were investigated using flow cytometry. Basal cytokine production by iPMLC compared to AM following their isolation from BAL fluid and the responsiveness of both cell types following in vitro treatment with the synthetic corticosteroid dexamethasone were assessed. rPMLC have a significantly increased expression of mature macrophage markers and of the proliferation antigen Ki67, compared to iPMLC. Our cytokine data revealed a pro-inflammatory, corticosteroid-resistant phenotype of iPMLC in this model. These data emphasise the presence of functionally distinct subpopulations of the monocyte/macrophage lineage in the human lung in experimental acute lung inflammation.
    Journal of Inflammation 03/2014; 11(1):9. · 2.55 Impact Factor
  • Source
    American Journal of Respiratory and Critical Care Medicine 02/2014; 189(4):500-1. · 11.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rationale: The pathogenesis of chronic obstructive pulmonary disease is not fully understood. Objectives: To compare circulating endothelial progenitor cells in patients with chronic obstructive pulmonary disease to age, gender and cigarette smoking matched healthy controls. Methods and Measurements: Patients with chronic obstructive pulmonary disease (n=37) and healthy controls (n=19) were matched by age, gender and smoking status. Circulating hematopoietic progenitor cells (CD34+ or CD133+ mononuclear cells) and endothelial progenitor cells (CD34(+)KDR(+) or CD34(+)CD133(+)KDR(+) mononuclear cells) were quantified by flow cytometry. Endothelial cell-colony forming units from peripheral blood mononuclear cells were quantified in vitro and phenotypic analysis carried out using immunocytochemistry. Main Results: Patients with chronic obstructive pulmonary disease had more circulating mononuclear cells compared to controls (8.4±0.6 versus 5.9±0.4 x109 cells/L; P=0.02). CD34(+) hematopoietic progenitor cells were reduced as a proportion of mononuclear cells in patients compared to controls (0.99±0.12 versus 1.9±0.12%; P=0.02), however there were no differences in the absolute number of CD34+, CD34(+)KDR(+) or CD34(+)CD133(+)KDR(+) cells (P>0.05 for all). Endothelial cell-colony forming units were increased in patients with chronic obstructive pulmonary disease compared to controls (13.7±5.2 versus 2.7±0.9 colonies; P=0.048). Conclusions: In contrast to previous studies the number of circulating progenitor cells were not reduced in patients with chronic obstructive pulmonary disease compared with carefully matched controls. It seems unlikely that circulating endothelial progenitor cells or failure of angiogenesis play a central role in the development of emphysema.
    AJP Lung Cellular and Molecular Physiology 10/2013; · 3.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: GCs are highly effective in treating a wide range of inflammatory diseases but are limited in their ability to control neutrophilic lung inflammation in conditions such as COPD. Neutrophil apoptosis, a central feature of inflammation resolution, is delayed in response to microenvironmental cues, such as hypoxia and inflammatory cytokines, present at inflamed sites. GCs delay neutrophil apoptosis in vitro, and this may therefore limit the ability of GCs to control neutrophilic inflammation. This study assesses the effect GCs have on hypoxia- and inflammatory cytokine-induced neutrophil survival. Human neutrophils were treated with GCs in the presence or absence of GM-CSF or inflammatory macrophage-CM at a range of oxygen concentrations (21-1% oxygen). Neutrophil apoptosis and survival were assessed by flow cytometry and morphological analysis and neutrophil function, by stimulus-induced shape change and respiratory burst. Dexamethasone promoted neutrophil survival at 21%, 10%, and 5% oxygen but not at 1% oxygen. Interestingly, GM-CSF and inflammatory CM increased neutrophil survival significantly, even at 1% oxygen, with cells remaining functionally active at 96 h. Dexamethasone was able to reduce the prosurvival effect of GM-CSF and inflammatory CM in a hypoxic environment. In conclusion, we found that GCs do not augment neutrophil survival in the presence of severe hypoxia or proinflammatory mediators. This suggests that GCs would not promote neutrophil survival at sites of inflammation under these conditions.
    Journal of leukocyte biology 08/2013; · 4.99 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: /st>Nosocomial infection occurs commonly in intensive care units (ICUs). Although critical illness is associated with immune activation, the prevalence of nosocomial infections suggests concomitant immune suppression. This study examined the temporal occurrence of immune dysfunction across three immune cell types, and their relationship with the development of nosocomial infection. METHODS: /st>A prospective observational cohort study was undertaken in a teaching hospital general ICU. Critically ill patients were recruited and underwent serial examination of immune status, namely percentage regulatory T-cells (Tregs), monocyte deactivation (by expression) and neutrophil dysfunction (by CD88 expression). The occurrence of nosocomial infection was determined using pre-defined, objective criteria. RESULTS: /st>Ninety-six patients were recruited, of whom 95 had data available for analysis. Relative to healthy controls, percentage Tregs were elevated 6-10 days after admission, while monocyte HLA-DR and neutrophil CD88 showed broader depression across time points measured. Thirty-three patients (35%) developed nosocomial infection, and patients developing nosocomial infection showed significantly greater immune dysfunction by the measures used. Tregs and neutrophil dysfunction remained significantly predictive of infection in a Cox hazards model correcting for time effects and clinical confounders {hazard ratio (HR) 2.4 [95% confidence interval (CI) 1.1-5.4] and 6.9 (95% CI 1.6-30), respectively, P=0.001}. Cumulative immune dysfunction resulted in a progressive risk of infection, rising from no cases in patients with no dysfunction to 75% of patients with dysfunction of all three cell types (P=0.0004). CONCLUSIONS: /st>Dysfunctions of T-cells, monocytes, and neutrophils predict acquisition of nosocomial infection, and combine additively to stratify risk of nosocomial infection in the critically ill.
    BJA British Journal of Anaesthesia 06/2013; · 4.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rationale: Depletion of monocytes reduces lipopolysaccharide-induced lung inflammation in mice, suggesting monocytes as potential therapeutic targets in acute lung injury. Objectives: To investigate whether depletion of circulating blood monocytes has beneficial effects on markers of systemic and pulmonary inflammation in a human model of acute lung inflammation. Methods: Thirty healthy volunteers were enrolled in a randomized controlled trial. Volunteers inhaled lipopolysaccharide at baseline and were randomized to receive active mononuclear cell depletion by leukapheresis, or sham leukapheresis, in a double-blind fashion (15 volunteers per group). Serial blood counts were measured, bronchoalveolar lavage was performed at 9 hours, and [18F]fluorodeoxyglucose positron emission tomography at 24 hours. The primary end-point was the increment in circulating neutrophils at 8 hours. Measurements and Main Results: As expected, inhalation of lipopolysaccharide induced neutrophilia and an up-regulation of inflammatory mediators in the blood and lungs of all volunteers. There was no significant difference between the depletion and sham groups in the mean increment in blood neutrophil count at 8 hours (6.16 x109/L and 6.15 x109/L respectively, P=1.00). Furthermore, there were no significant differences in bronchoalveolar lavage neutrophils or protein, positron emission tomography-derived measures of global lung inflammation or cytokine levels in plasma or bronchoalveolar lavage supernatant between the study groups. No serious adverse events occurred, and no symptoms were significantly different between the groups. Conclusions: These findings do not support a role for circulating human monocytes in the early recruitment of neutrophils during lipopolysaccharide-mediated acute lung inflammation in humans.
    American Journal of Respiratory and Critical Care Medicine 04/2013; · 11.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A decade of research has sought to identify circulating endothelial progenitor cells (EPC) in order to harness their potential for cardiovascular regeneration. Endothelial outgrowth cells (EOC) most closely fulfil the criteria for an EPC, but their origin remains obscure. Our aim was to identify the source and precursor of EOC and to assess their regenerative potential compared to mature endothelial cells. EOC are readily isolated from umbilical cord blood (6/6 donors) and peripheral blood mononuclear cells (4/6 donors), but not from bone marrow (0/6) nor peripheral blood following mobilisation with granulocyte-colony stimulating factor (G-CSF) (0/6 donors). Enrichment and depletion of blood mononuclear cells demonstrated that EOC are confined to the CD34(+) CD133(-) CD146(+) cell fraction. EOC derived from blood mononuclear cells are indistinguishable from mature human umbilical vein endothelial cells (HUVEC) by morphology, surface antigen expression, immunohistochemistry, real-time polymerase chain reaction (RT-PCR), proliferation and functional assessments. In a subcutaneous sponge model of angiogenesis, both EOC and HUVEC contribute to de novo blood vessel formation giving rise to a similar number of vessels (7.0±2.7 versus 6.6±3.7 vessels respectively, n=9. Bone marrow-derived outgrowth cells isolated under the same conditions expressed mesenchymal markers rather than endothelial cell markers and did not contribute to blood vessels in vivo. In this paper, we confirm that EOC arise from CD34(+) CD133(-) CD146(+) mononuclear cells and are similar, if not identical, to mature endothelial cells. Our findings suggest that EOC do not arise from bone marrow and challenge the concept of a bone marrow-derived circulating precursor for endothelial cells.
    Stem Cells 11/2012; · 7.70 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and Objectives  There is increasing evidence that monocytes play a key role in the pathogenesis of acute lung inflammation. Mononuclear cell (MNC) leukapheresis can be used to remove large numbers of monocytes from circulating blood; however, the detailed characteristics of monocyte subpopulations removed by MNC leukapheresis, and the biological effects on the lung, remain incompletely defined. Material and Methods  Six healthy male volunteers underwent MNC leukapheresis of four total blood volumes. Blood was collected at 0, 2, 4, 6, 8 and 24 h; bronchoscopy with bronchoalveolar lavage (BAL) was performed at 8-9 h. Multiparameter flow cytometry was used to identify subpopulations of monocytes in blood and monocyte-like cells in BAL fluid. Results  A median of 5·57 × 10(9) monocytes were retrieved. Blood monocyte counts indicated that the circulating blood monocyte pool was actively replenished during leukapheresis and subsequently contained a greater proportion of classical (CD14(++ ) CD16(-) ) monocytes. A particular subpopulation of monocyte-like cells, reminiscent of classical monocytes, was also prominent in BAL fluid after leukapheresis. Conclusion  Mononuclear cell leukapheresis was safe. The greater proportion of classical monocytes present in blood after MNC leukapheresis may be clinically significant. MNC leukapheresis also appears to affect the proportion of monocyte-like cells in the lung; however, we found no evidence that leukapheresis has a clinically important pro-inflammatory effect in the human lung.
    Vox Sanguinis 04/2012; 103(4):275-83. · 2.85 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The co-ordinated recruitment of monocyte subpopulations, neutrophils and regulatory T-cells (Tregs) during the early stages of human acute lung inflammation remains poorly understood. We therefore performed a detailed characterisation of these lineages in the blood and lungs in a model of human acute lung inflammation. Healthy volunteers inhaled lipopolysaccharide (LPS) or saline (n=6 for each group). Blood was collected at 0, 2, 4, 6 and 8 h and bronchoscopy with bronchoalveolar lavage (BAL) performed at 8 h. Multiparameter flow cytometry was used to characterise monocyte subpopulations, neutrophils and Tregs in the blood and lung. Inhalation of LPS was associated with significant blood and BAL fluid neutrophilia. Blood populations of monocyte subpopulations and Tregs were unaltered by LPS. In contrast, LPS induced an accumulation of a pulmonary monocyte-like cell (PMLC) population, which was further subdivided into "inducible" CD14(++)CD16(-) and "resident" CD14(++)CD16(+) subsets. Inducible PMLCs were significantly increased following LPS inhalation (p=0.0046), whereas resident PMLCs were unchanged. In addition, we noted a significant decrease in Tregs in BAL fluid with LPS inhalation (p=0.027). The early stages of LPS-induced inflammation in humans is characterised by pulmonary accumulation of a novel inducible monocyte-like subpopulation, accompanied by significant changes in both neutrophil and Treg numbers.
    European Respiratory Journal 01/2012; 40(1):206-14. · 6.36 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Critically ill patients are at heightened risk for nosocomial infections. The anaphylatoxin C5a impairs phagocytosis by neutrophils. However, the mechanisms by which this occurs and the relevance for acquisition of nosocomial infection remain undetermined. We aimed to characterize mechanisms by which C5a inhibits phagocytosis in vitro and in critically ill patients, and to define the relationship between C5a-mediated dysfunction and acquisition of nosocomial infection. In healthy human neutrophils, C5a significantly inhibited RhoA activation, preventing actin polymerization and phagocytosis. RhoA inhibition was mediated by PI3Kδ. The effects on RhoA, actin, and phagocytosis were fully reversed by GM-CSF. Parallel observations were made in neutrophils from critically ill patients, that is, impaired phagocytosis was associated with inhibition of RhoA and actin polymerization, and reversed by GM-CSF. Among a cohort of 60 critically ill patients, C5a-mediated neutrophil dysfunction (as determined by reduced CD88 expression) was a strong predictor for subsequent acquisition of nosocomial infection (relative risk, 5.8; 95% confidence interval, 1.5-22; P = .0007), and remained independent of time effects as assessed by survival analysis (hazard ratio, 5.0; 95% confidence interval, 1.3-8.3; P = .01). In conclusion, this study provides new insight into the mechanisms underlying immunocompromise in critical illness and suggests novel avenues for therapy and prevention of nosocomial infection.
    Blood 02/2011; 117(19):5178-88. · 9.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: beta3-Integrin is a cell surface adhesion and signalling molecule important in the regulation of tumour angiogenesis. Mice with a global deficiency in beta3-integrin show increased pathological angiogenesis, most likely due to increased vascular endothelial growth factor receptor 2 expression on beta3-null endothelial cells. Here we transplanted beta3-null bone marrow (BM) into wild-type (WT) mice to dissect the role of BM beta3-integrin deficiency in pathological angiogenesis. Mice transplanted with beta3-null bone marrow show significantly enhanced angiogenesis in subcutaneous B16F0 melanoma and Lewis lung carcinoma (LLC) cell models and in B16F0 melanoma lung metastasis when compared with tumours grown in mice transplanted with WT bone marrow. The effect of bone marrow beta3-integrin deficiency was also assessed in the RIPTAg mouse model of pancreatic tumour growth. Again, angiogenesis in mice lacking BM beta3-integrin was enhanced. However, tumour weight between the groups was not significantly altered, suggesting that the enhanced blood vessel density in the mice transplanted with beta3-null bone marrow was not functional. Indeed, we demonstrate that in mice transplanted with beta3-null bone marrow a significant proportion of tumour blood vessels are non-functional when compared with tumour blood vessels in WT-transplanted controls. Furthermore, beta3-null-transplanted mice showed an increased angiogenic response to VEGF in vivo when compared with WT-transplanted animals. BM beta3-integrin deficiency affects the mobilization of progenitor cells to the peripheral circulation. We show that VEGF-induced mobilization of endothelial progenitor cells is enhanced in mice transplanted with beta3-null bone marrow when compared with WT-transplanted controls, suggesting a possible mechanism underlying the increased blood vessel density seen in beta3-null-transplanted mice. In conclusion, although BM beta3-integrin is not required for pathological angiogenesis, our studies demonstrate a role for BM beta3-integrin in VEGF-induced mobilization of bone marrow-derived cells to the peripheral circulation and for the functionality of those vessels in which BM-derived cells become incorporated.
    The Journal of Pathology 10/2009; 220(4):435-45. · 7.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Endothelial progenitor cells (EPCs) in bone marrow (BM) and peripheral blood (PB) contribute to tissue repair in various pathological conditions via the formation of new blood vessels. Previous studies indicate that diabetic patients have reduced EPC number and deregulated EPC function, although the regenerative properties of EPCs in diabetes are unknown. We wish to characterize and compare EPCs from pre-diabetic and diabetic non-obese diabetic (NOD) mice, a model of type 1 diabetes (T1D), in order to delineate the role of these cells in the pathogenesis of autoimmune diabetes. Whole BM was obtained by flushing femurs, tibias and illiac crests from pre-diabetic and diabetic NOD mice (5-30 weeks) in which the diabetic status was confirmed by measuring blood glucose levels (> or =11.5 mmol/L); PB was collected in heparin-coated tubes and lysed after incubation with antibodies directed against EPCs. FACS analyses revealed a significant decrease in EPC number (CD31(+), c-Kit(+), Sca-1(+), Lin(-)) in BM from diabetic compared to pre-diabetic mice (P = 0.02). Conversely, EPC number was significantly increased in PB from diabetic compared to pre-diabetic mice (P = 0.01). These data suggest that at the onset of diabetes, BM-derived EPCs are stimulated to enter the systemic circulation likely in response to signals from the pancreas. Further studies are required to elucidate whether EPCs home the damaged pancreas, thus representing a prospective source of autologous cells for beta-cell regeneration therapy.
    Diabetes/Metabolism Research and Reviews 01/2009; 25(1):89-93. · 2.97 Impact Factor
  • Wey-Ran Lin, Mairi Brittan, Malcolm R Alison
    [Show abstract] [Hide abstract]
    ABSTRACT: There is a growing realization that bone marrow-derived cells (BMDCs) are a potential therapy for many diseases including ischemic heart disease, arterial stenosis and osteogenesis imperfecta. On the other hand, the fact that BMDCs may also contribute to fibrosis in many solid organs as well as to fibrosis surrounding tumours suggests that BMDCs are also involved in disease progression. This review focuses on the contribution of bone marrow cells to organ and tumour fibrosis, noting the utility of BMDCs as a potential new portal through which to direct anti-tumour therapies. Conversely, bone marrow cell therapy has been claimed to reduce fibrosis in some organs, highlighting a seemingly beneficial as opposed to a detrimental effect of BMDCs on organ fibrosis.
    Cells Tissues Organs 02/2008; 188(1-2):178-88. · 1.96 Impact Factor
  • D Mizrak, M Brittan, M R Alison
    [Show abstract] [Hide abstract]
    ABSTRACT: CD133 (prominin-1) was the first in a class of novel pentaspan membrane proteins to be identified in both humans and mice, and was originally classified as a marker of primitive haematopoietic and neural stem cells. Due to the highly restricted expression of CD133 family molecules on plasma membrane protrusions of epithelial and other cell types, in association with membrane cholesterol, a role in the organization of plasma membrane topology has also recently been assigned to this family. Studies have now confirmed the utility of CD133 as a marker of haematopoietic stem cells for human allogeneic transplantation. In addition, CD133 represents a marker of tumour-initiating cells in a number of human cancers, and therefore it may be possible to develop future therapies towards targeting cancer stem cells via this marker. The development of such therapies will be aided by a clearer understanding of the molecular mechanisms and signalling pathways that regulate the behaviour of CD133-expressing cells, and new data outlining the role of Wnt, Notch, and bone morphogenetic protein (BMP) signalling in CD133(+) cancer stem cell regulation are discussed within.
    The Journal of Pathology 02/2008; 214(1):3-9. · 7.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Complex biomolecules absorb in the mid-infrared (λ = 2–20 μm), giving vibrational spectra associated with structure and function. We used Fourier transform infrared (FTIR) microspectroscopy to “fingerprint” locations along the length of human small and large intestinal crypts. Paraffin-embedded slices of normal human gut were sectioned (10 μm thick) and mounted to facilitate infrared (IR) spectral analyses. IR spectra were collected using globar (15 μm × 15 μm aperture) FTIR microspectroscopy in reflection mode, synchrotron (≤10 μm × 10 μm aperture) FTIR microspectroscopy in transmission mode or near-field photothermal microspectroscopy. Dependent on the location of crypt interrogation, clear differences in spectral characteristics were noted. Epithelial-cell IR spectra were subjected to principal component analysis to determine whether wavenumber-absorbance relationships expressed as single points in “hyperspace” might on the basis of multivariate distance reveal biophysical differences along the length of gut crypts. Following spectroscopic analysis, plotted clusters and their loadings plots pointed toward symmetric (νs)PO2− (1,080 cm−1) vibrations as a discriminating factor for the putative stem cell region; this proved to be a more robust marker than other phenotypic markers, such as β-catenin or CD133. This pattern was subsequently confirmed by image mapping and points to a novel approach of nondestructively identifying a tissue's stem cell location. νsPO2−, probably associated with DNA conformational alterations, might facilitate a means of identifying stem cells, which may have utility in other tissues where the location of stem cells is unclear.Disclosure of potential conflicts of interest is found at the end of this article.
    Stem Cells 12/2007; 26(1):108 - 118. · 7.70 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Inflammatory bowel disease (IBD) is characterized by an ongoing mucosal inflammation caused by a dysfunctional host immune response to commensal microbiota and dietary factors. In the pathophysiology of IBD, mesenchymal cells such as intestinal subepithelial myofibroblasts (ISEMF) affect the recruitment, retention and activation of immune cells. Mesenchymal cells also promote resolution of inflammatory activity accompanied with balanced repair processes. The transient appearance of mesenchymal cells is a feature of normal wound healing, but the persistence of these cells is associated with tissue fibrosis. Recent studies suggest that mesenchymal cells derived from bone marrow (BM) stem cells play a crucial role in intestinal repair and fibrosis. This article focuses on recent knowledge about ISEMF in the field of immune response inflammation and repair. Two major topics were documented: interaction between interleukin (IL)-17-secreting CD4+ cells (Th-17 cells) and about role of BM-derived stem cells in mucosal regenerative response via differentiation to ISEMF. Recent therapeutic strategies targeting BM stem cells for IBD patients were also documented.
    Pharmacology [?] Therapeutics 05/2007; 114(1):94-106. · 7.79 Impact Factor
  • Gastroenterology 04/2007; 132(3):1171-3. · 12.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the twenty-first century, diabetic patients are likely to be one of the major beneficiaries from the advancement of regenerative medicine through cellular therapies. Though the existence of a specific self-renewing stem cell within the pancreas is still far from clear, a surprising variety of cells within the pancreas can differentiate towards a beta-cell phenotype: ductular cells, periductular mesenchymal cells and beta-cells themselves can all give rise to new beta-cells. Extra-pancreatic adult somatic stem cells, in particular, those originating from bone marrow may also be capable of differentiating to beta-cells, though equally well the beneficial effects of bone marrow cells may reside in their contribution to the damaged islet vasculature. Forced expression of the beta-cell-specific transcription factor Pdx1 in hepatocytes also holds promise as a therapeutic strategy to increase insulin levels in diabetic individuals. Embryonic stem (ES) cells are clearly another possible source for generating beta-cells, but ES cells are beyond the scope of this review, which focuses on adult stem and progenitor cells capable of producing beta-cells. Despite considerable endeavour, we still have much to learn in the field of pancreatic regeneration prior to any clinically applicable therapy based upon adult stem cells.
    Diabetes/Metabolism Research and Reviews 03/2007; 23(2):87-99. · 2.97 Impact Factor

Publication Stats

2k Citations
283.56 Total Impact Points

Institutions

  • 2011–2013
    • The University of Edinburgh
      • Queen's Medical Research Institute
      Edinburgh, SCT, United Kingdom
  • 2012
    • Newcastle University
      Newcastle-on-Tyne, England, United Kingdom
  • 2006–2007
    • Shiga University of Medical Science
      • Department of Gastroenterology
      Ōtu, Shiga, Japan
    • Queen Mary, University of London
      • The Blizard Institute of Cell and Molecular Science
      London, ENG, United Kingdom
  • 2005
    • London Research Institute
      Londinium, England, United Kingdom
  • 2003–2005
    • Cancer Research UK
      Londinium, England, United Kingdom
    • Imperial College London
      Londinium, England, United Kingdom
  • 2004
    • University College London
      • Molecular Immunology unit
      London, ENG, United Kingdom
  • 1999
    • University of Glasgow
      Glasgow, Scotland, United Kingdom