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Cáceres, Spain

Sanchez-Correa B.,University of Extremadura | Campos C.,University of Cordoba, Spain | Pera A.,University of Cordoba, Spain | Bergua J.M.,Hospital San Pedro de Alcantara | And 8 more authors.
Cancer Immunology, Immunotherapy

Several age-associated changes in natural killer (NK) cell phenotype have been reported that contribute to the defective NK cell response observed in elderly patients. A remodelling of the NK cell compartment occurs in the elderly with a reduction in the output of immature CD56bright cells and an accumulation of highly differentiated CD56dim NK cells. Acute myeloid leukaemia (AML) is generally a disease of older adults. NK cells in AML patients show diminished expression of several activating receptors that contribute to impaired NK cell function and, in consequence, to AML blast escape from NK cell immunosurveillance. In AML patients, phenotypic changes in NK cells have been correlated with disease progression and survival. NK cell-based immunotherapy has emerged as a possibility for the treatment of AML patients. The understanding of age-associated alterations in NK cells is therefore necessary to define adequate therapeutic strategies in older AML patients. © 2015 Springer-Verlag Berlin Heidelberg Source

Sanchez-Correa B.,University of Extremadura | Bergua J.M.,Hospital San Pedro de Alcantara | Campos C.,University of Cordoba, Spain | Gayoso I.,University of Cordoba, Spain | And 7 more authors.

Background: Several evidences support the existence of cytokine deregulation in acute myeloid leukemia (AML) patients that may be associated with pathogenesis, disease progression and patient survival. Methods: In the present study, we analyzed plasma levels of pro- and anti-inflammatory cytokines in AML patients and age-matched healthy donors. TNF-α, IL-6, IL-1β, IL-2, IFN-γ, IL-17A, IL-12p70, IL-8, IL-10, IL-4 and IL-5 were analyzed using fluorescent bead-based technology and TGF-β by ELISA technique. Because age-associated differences in cytokine profiles have been described, patients and healthy individuals were divided into two age groups: up to 65. years and over 65. years. Results: Our results showed that plasma TNF-α, IL-6 and IL-10 levels were higher in AML patients from both groups of age. IL-8 was increased in AML patients less than 65. years while the plasma concentrations of IL-4, IL-5 and IL-12p70 were significantly higher only in elderly AML patients compared with aged-matched healthy controls. Moreover, plasma levels of IL-6 and IL-10 were associated with patient survival and event-free survival. Conclusions: An aberrant production of the pro-inflammatory cytokines IL-6 and TNF-α and the anti-inflammatory cytokine IL-10 is observed in AML patients. Low levels of IL-6 and high levels of IL-10 represent favorable prognostic factors for survival in AML patients. These results support the idea that cytokine deregulation may be useful as a marker for predicting clinical evolution in AML patients. © 2013 Elsevier Ltd. Source

Blazquez R.,Stem Cell Therapy Unit | Sanchez-Margallo F.M.,Stem Cell Therapy Unit | de la Rosa O.,TiGenix | Dalemans W.,TiGenix | And 3 more authors.
Frontiers in Immunology

In the recent years, it has been demonstrated that the biological activity of mesenchymal stem cells (MSCs) is mediated through the release of paracrine factors. Many of these factors are released into exosomes, which are small membranous vesicles that participate in cell-cell communication. Exosomes from MSCs are thought to have similar functions to MSCs such as repairing and regeneration of damaged tissue, but little is known about the immunomodulatory effect of these vesicles. Based on an extensive bibliography where the immunomodulatory capacity of MSCs has been demonstrated, here we hypothesized that released exosomes from MSCs may have an immunomodulatory role on the differentiation, activation and function of different lymphocyte subsets. According to this hypothesis, in vitro experiments were performed to characterize the immunomodulatory effect of human adipose MSCs derived exosomes (exo-hASCs) on in vitro stimulated T cells. The phenotypic characterization of cytotoxic and helper T cells (activation and differentiation markers) together with functional assays (proliferation and IFN-γ production) demonstrated that exo-hASCs exerted an inhibitory effect in the differentiation and activation of T cells as well as a reduced T cell proliferation and IFN-γ release on in vitro stimulated cells. In summary, here we demonstrate that MSCs-derived exosomes are a cell-derived product that could be considered as a therapeutic agent for the treatment of inflammation-related diseases. © 2014 Blazquez, Sanchez-Margallo, de la Rosa, Dalemans, Álvarez, Tarazona and Casado. Source

Casado J.G.,Stem Cell Therapy Unit | Tarazona R.,University of Extremadura | Sanchez-Margallo F.M.,Stem Cell Therapy Unit
Stem Cell Reviews and Reports

Several clinical trials are currently evaluating the safety and efficacy of mesenchymal stem cells (MSCs) in different diseases. The MSCs are guided by inflammatory mediators and specific interactions with immune cells occur, especially between MSCs and the cells of the innate immune system. At the present many of these interactions remain to be determined. This review summarizes the current knowledge in relation to the susceptibility of MSCs to NK cell mediated lysis as well as the immunomodulatory activity of MSCs and its control over NK cell function. Here we hypothesize that the inflammatory context will regulate the outcome of NK-MSC interactions. © 2013 Springer Science+Business Media New York. Source

Blazquez R.,Stem Cell Therapy Unit | Sanchez-Margallo F.M.,Stem Cell Therapy Unit | Crisostomo V.,Minimally Invasive Surgery Center | Baez C.,Minimally Invasive Surgery Center | And 5 more authors.

The appropriate administration route for cardiovascular cell therapy is essential to ensure the viability, proliferative potential, homing capacity and implantation of transferred cells. At the present, the intrapericardial administration of pharmacological agents is considered an efficient method for the treatment of cardiovascular diseases. However, only a few reports have addressed the question whether the intrapericardial delivery of Mesenchymal Stem Cells (MSCs) could be an optimal administration route. This work firstly aimed to analyze the pericardial fluid as a cell-delivery vehicle. Moreover, the in vivo biodistribution pattern of intrapericardially administered MSCs was evaluated in a clinically relevant large animal model. Our in vitro results firstly showed that, MSCs viability, proliferative behavior and phenotypic profile were unaffected by exposure to pericardial fluid. Secondly, in vivo cell tracking by magnetic resonance imaging, histological examination and Y-chromosome amplification clearly demonstrated the presence of MSCs in pericardium, ventricles (left and right) and atrium (left and right) when MSCs were administered into the pericardial space. In conclusion, here we demonstrate that pericardial fluid is a suitable vehicle for MSCs and intrapericardial route provides an optimal retention and implantation of MSCs. © 2015 Blázquez et al. Source

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