Oral mucosal progenitor cells are potently immunosuppressive in a dose-independent manner.

Oral mucosal lamina propria progenitor cells (OMLP-PCs) are a novel, clonally derived PC population of neural crest origin with the potential to differentiate down both mesenchymal and neuronal cell lineages. In this study we aimed to determine the immunological properties of OMLP-PCs and to establish whether they would be suitable candidates for allogeneic tissue engineering and in the treatment of immune-related diseases. OMLP-PCs demonstrated no inherent immunogenicity with insignificant expression of costimulatory molecules (CD40, CD80, CD86, CD154, and CD178) or human leukocyte antigen (HLA) class II. OMLP-PCs required 7 days of stimulation with interferon-γ (IFN-γ) to induce cell surface expression of HLA II. Mixed lymphocyte cultures and mitogen stimulation demonstrated the potent immunosuppressive capability of OMLP-PCs in a contact-independent manner. Complete inhibition of lymphocyte proliferation was seen at doses as low as 0.001% OMLP-PCs to responder lymphocytes, while annexin V staining confirmed that this immunosuppressive effect was not due to the induction of lymphocyte apoptosis. These data demonstrate, for the first time, that OMLP-PC immunomodulation, unlike that for mesenchymal stem cells, occurs via a dose- and HLA II-independent mechanism by the release of immunosuppressive soluble factors and suggests these cells may have wide ranging potential in future immune-related therapies.

Implant periapical lesion. A case series report.

One complication in implant dentistry is the implant periapical lesion-IPL--which is a lesion around the apex of a stable implant diagnosed radiographically as a radioluscency in the bone at the apical part of an implant.The IPL can perform with or without clinical symptoms such as tenderness, swelling, suppuration and fistulation. This report describes 4 cases of IPL which were treated surgically with sectioning and removal of the affected portion of a stable implant and thorough debridement of the granulomatous tissue around it. This treatment was, up to 4 years after treatment, successful in all 4 cases. It can also from this report be concluded that IPL is a rather rare condition and that it can occur at any stage of implant treatment, in these cases from 4 months up to 11 years after implant installation. Finally there is a discussion about the aetiology of IPL and a comparison to findings in other reports on IPL and it is concluded that it is difficult to claim that there is a single cause to IPL. Rather it is evident that the condition might be a sequel of the summation of many possible causes.This summation exceeds the local biological threshold for the individual patient.

Effects of carbon monoxide poisoning on neutrophil responses in patients treated with hyperbaric oxygen.

BACKGROUND: Carbon monoxide (CO) poisoning can cause tissue injury. Neutrophil granulocytes have been proposed to contribute to the injury, which may be ameliorated by hyperbaric oxygen (HBO2) treatment. We sought to assess the relationship between acute CO poisoning and blood neutrophil count, plasma cytokine, and cortisol responses, as well as the mechanism behind the observed beneficiary effects of HBO2 treatment. METHODS: Eight patients (age 26-82 years) with severe acute CO poisoning were enrolled, concomitant with eight healthy controls (age 27-42 years), in a prospective, controlled, clinical study. The patients were given three HBO2 treatments (2.8 atmospheres absolute, 100 minutes) within the first 24 hours. The controls were given identical simultaneous HBO2 treatments. Venous blood samples were taken before and after each treatment. RESULTS: At the start of the HBO2 treatment, patients displayed significantly higher blood neutrophil counts (p < .0001) and plasma cortisol levels (p = .020) than controls, but the two groups had similar values for interleukin-8, granulocyte colony-stimulating factor (G-CSF), neutrophil H2O2 generation, and CD16 and CD18 surface expression. During the observation time, neutrophil H2O2 accumulation declined in patients and in controls (p = .031), whereas the up-regulation of CD18 expression increased (p = .002) in both groups. Moreover, G-CSF levels became significantly higher in patients than in controls (p = .015). G-CSF levels also correlated significantly with neutrophil counts. CONCLUSION: CO poisoning was associated with discrete changes of blood neutrophil counts, cortisol, and G-CSF plasma concentrations. HBO2 treatment modulated neutrophil generation of H2O2 and surface expression of CD18. These changes may be part of the cascade of events leading to the sequelae of CO poisoning and their attenuation by HBO2.

HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells.

OBJECTIVE: Mesenchymal stem cells (MSC) do not elicit alloreactive lymphocyte responses due to immune modulations. We investigated the immunologic properties of MSC after differentiation along three lineages: bone, cartilage, and adipose. METHODS AND RESULTS: Flow cytometry showed that undifferentiated MSC express HLA class I but not class II, although HLA class II was present intracellularly as detected by Western blot. Addition of interferon gamma (IFN-gamma) for 48 hours induced greater than 90% of cells to express HLA class II. No lymphocyte response was induced by allogeneic irradiated MSC as stimulators. Results were similar using MSC pretreated with IFN-gamma. After growth of cells in medium to induce differentiation to bone, cartilage, or adipose for 6 or 12 days, the expression of HLA class I increased but no class II was detected on the cell surface. The ability to upregulate HLA class II on the cell surface after exposure to IFN-gamma for 48 hours was clearly diminished after the cells had been cultured in differentiation medium for 6 or 12 days, with only 10% of cells expressing HLA class II. Using MSC grown in osteogenic, chondrogenic, or adipogenic medium as stimulator cells, no lymphocyte alloreactivity was seen, even if differentiated MSC had been pretreated with IFN-gamma. MSC inhibit mixed lymphocyte cultures, particularly after osteogenic differentiation. This suppression was further enhanced by IFN-gamma. CONCLUSIONS: Undifferentiated and differentiated MSC do not elicit alloreactive lymphocyte proliferative responses and modulate immune responses. The findings support that MSC can be transplantable between HLA-incompatible individuals.