Physiological and pathological consequences of identification of very small embryonic like (VSEL) stem cells in adult bone marrow.
ABSTRACT Bone marrow (BM) contains a population of self-renewing hematopoietic stem cells (HSC) that give rise to cells from all hemato-lymphopoietic lineages. The concept that HSC could also be plastic and be able to transdifferentiate into stem/progenitor cells for different non-hematopoietic tissues became one of the most controversial issues of modern stem cell biology. Accumulating experimental evidence suggests that contribution of BM-derived stem cells to organ/tissue regeneration could be explained not by plasticity (transdifferentiation) of HSC but rather by the presence of non-hematopoietic stem cells in BM. In this review new evidence will be presented, that adult BM contains a small population of pluripotent very small embryonic-like (VSEL) stem cells. These cells are deposited in BM early during ontogenesis and could be mobilized from BM and circulate in peripheral blood during tissue/organ injury in an attempt to regenerate damaged organs. However, if these cells are mobilized at the wrong time and migrate to the wrong place they may contribute to the development of several pathologies, including tumor formation.
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ABSTRACT: Stimulating lymphocytes with Ifn-γ, anti-CD3, and interleukin-2 promotes the proliferation of a cell population coexpressing T-lymphocyte surface antigens such as CD3, CD8a, and CD25 as well as natural killer cell markers such as NK1.1, CD49, and CD69. These cells, referred to as cytokine-induced killer cells (CIKs), display cytotoxic activity against tumour cells, even without prior antigen presentation, and offer a new cell-based approach to the treatment of malignant diseases. Because CIKs are limited in vivo, strategies to optimize in vitro culture yield are required. In the last 10 years, mesenchymal stem cells (MSCs) have gathered considerable attention. Aside from their uses in tissue engineering and as support in haematopoietic stem cell transplantations, MSCs show notable immunomodulatory characteristics, providing further possibilities for therapeutic applications. In this study, we investigated the influence of murine MSCs on proliferation, phenotype, vitality, and cytotoxicity of murine CIKs in a coculture system. We found that CIKs in coculture proliferated within 7 days, with an average growth factor of 18.84, whereas controls grew with an average factor of 3.7 in the same period. Furthermore, higher vitality was noted in cocultured CIKs than in controls. Cell phenotype was unaffected by coculture with MSCs and, notably, coculture did not impact cytotoxicity against the tumour cells analysed. The findings suggest that cell-cell contact is primarily responsible for these effects. Humoral interactions play only a minor role. Furthermore, no phenotypical MSCs were detected after coculture for 4 h, suggesting the occurrence of immune reactions between CIKs and MSCs. Further investigations with DiD-labelled MSCs revealed that the observed disappearance of MSCs appears not to be due to differentiation processes.PLoS ONE 01/2014; 9(2):e88115. · 3.53 Impact Factor
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ABSTRACT: The exact prevalence of hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) remains unclear in patients with chronic rhinosinusitis (CRS) because many of these patients routinely avoid the use of NSAIDs. Since the diagnosis of aspirin hypersensitivity is based mainly on history, the aspirin challenge protocol is seldom used clinically in China. The objective of this study is to investigate the prevalence of NSAID hypersensitivity in Chinese patients diagnosed with CRS. In a unique cohort study, consecutive CRS patients received intramuscular diclofenac sodium injection or diclofenac sodium sustained-release tablets to relieve intraoperative and postoperative pain following nasal surgery. In addition, data on NSAID hypersensitivity in large-sample series of CRS patients were collected by searching relevant literature published in Chinese to determine the prevalence of NSAID hypersensitivity in Chinese patients with CRS. A total of 244 consecutive CRS patients were included in this study. Three (1.34 %) patients experienced a severe asthmatic attack after intramuscular diclofenac sodium injection and were diagnosed with NSAID hypersensitivity. Despite the use of different methods to diagnose NSAID hypersensitivity, the prevalence of NSAID hypersensitivity in Chinese CRS patients was between 0.28 and 1.46 %. The prevalence of NSAID hypersensitivity in Chinese patients with CRS is low, which is a distinct clinical characteristic of Chinese CRS patients. Despite the apparently low prevalence of the condition in this population, a large number of patients in China are affected by this disorder, which should not be overlooked or regarded with an indifferent attitude in medical research and clinical practices.Archives of Oto-Rhino-Laryngology 02/2014; · 1.29 Impact Factor
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ABSTRACT: Aspirin intolerance syndrome is due to disturbances in the arachidonic acid metabolism implicating both the lipoxygenase and cyclooxygenase pathways. This results in imbalances of eicosanoid, leukotriene and prostaglandin synthesis. Thus, preinflammatory cysteinyl leukotrienes increase and antiinflammatory prostaglandins (PG) such as PGE2 decrease. Clinically, intolerance reactions to nonsteroidal antiinflammatory drugs (NSAIDs) can lead to different clinical manifestations; five phenotypes of the aspirin intolerance syndrome are listed in the ENDA classification. Aspirin-exacerbated respiratory disease (AERD) is the most common phenotype characterized by an eosinophil-dominated inflammatory disease of the airways that presents clinically with nasal polyps, chronic sinusitis and bronchial asthma. About 34 % of patients with aspirin-induced asthma and rhinosinusitis are thought to have AERD. Important biochemical findings in many AERD patients are increased basal leukotriene levels (at least in cell cultures) that excessively increase after intake of COX-1 inhibitors. Aspirin desensitization uses the repetitive application of aspirin to induce a tolerance to NSAIDs, especially COX-1 inhibitors. After a dose-increase phase reaching a threshold dose, a dose-continuation phase is performed. For application, the nasal, bronchial, oral and intravenous routes have been described. Aspirin desensitization has been proven to be efficacious and safe and was able to reduce the need for other medications in AERD patients.Current Allergy and Asthma Reports 06/2014; 14(6):441. · 2.75 Impact Factor