Trasplante autólogo de médula ósea : Efectos sobre el injerto de la manipulación de las células hemopoyéticas y de las variables clínicas

El trasplante autólogo de médula ósea es una técnica utilizada para el tratamiento de ciertas enfermedades oncohematologicas, y que consiste en la aplicación de altas dosis de quimio y/o radioterapia, seguida de un rescate con células germinales obtenidas de medula ósea, que reconstituyen la hemopoyesis. La médula ósea obtenida en quirófano es sometida a procesos de fraccionamiento y criopreservacion, que pueden afectar al contenido de progenitores, y por lo tanto al injerto. En esta memoria hemos analizado las características del inoculo medular antes y después de estos procedimientos. Por otra parte hemos estudiado de que forma se ve afectado el injerto según la cantidad de progenitores infundidos en el momento del trasplante, asi como de la influencia en el mismo de variables como los periodos de tiempo desde el diagnostico hasta el trasplante, o características clínicas de los pacientes, como el diagnostico y el estatus de la enfermedad. Los estudios realizados pusieron de manifiesto que tras las manipulaciones medulares realizadas se obtuvo un producto que garantizo, en todos los casos de esta serie, el injerto del inoculo medular. Por otra parte, ninguno de los aspectos clínicos de los pacientes analizados en esta serie, influyeron en el injerto, a excepción de los pacientes con diagnostico leucemia mieloblastica, que presentaron un injerto demorado con respecto a los demás pacientes, independientemente de otras variables que podrían influir

Enhanced anti-inflammatory effects of mesenchymal stromal cells mediated by the transient ectopic expression of CXCR4 and IL10

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliationsBackground Mesenchymal stromal cells (MSCs) constitute one of the cell types most frequently used in cell therapy. Although several studies have shown the efficacy of these cells to modulate inflammation in different animal models, the results obtained in human clinical trials have been more modest. Here, we aimed at improving the therapeutic properties of MSCs by inducing a transient expression of two molecules that could enhance two different properties of these cells. With the purpose of improving MSC migration towards inflamed sites, we induced a transient expression of the C-X-C chemokine receptor type 4 (CXCR4). Additionally, to augment the anti-inflammatory properties of MSCs, a transient expression of the anti-inflammatory cytokine, interleukin 10 (IL10), was also induced. Methods Human adipose tissue-derived MSCs were transfected with messenger RNAs carrying the codon-optimized versions of CXCR4 and/or IL10. mRNA-transfected MSCs were then studied, first to evaluate whether the characteristic phenotype of MSCs was modified. Additionally, in vitro and also in vivo studies in an LPS-induced inflamed pad model were conducted to evaluate the impact associated to the transient expression of CXCR4 and/or IL10 in MSCs. Results Transfection of MSCs with CXCR4 and/or IL10 mRNAs induced a transient expression of these molecules without modifying the characteristic phenotype of MSCs. In vitro studies then revealed that the ectopic expression of CXCR4 significantly enhanced the migration of MSCs towards SDF-1, while an increased immunosuppression was associated with the ectopic expression of IL10. Finally, in vivo experiments showed that the co-expression of CXCR4 and IL10 increased the homing of MSCs into inflamed pads and induced an enhanced anti-inflammatory effect, compared to wild-type MSCs. Conclusions Our results demonstrate that the transient co-expression of CXCR4 and IL10 enhances the therapeutic potential of MSCs in a local inflammation mouse model, suggesting that these mRNA-modified cells may constitute a new step in the development of more efficient cell therapies for the treatment of inflammatory diseasesThis work was supported by the following public grants: Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III Ministerio de Ciencia, Innovación y Universidades and Fondo Europeo de Desarrollo Regional (FEDER) ((RETICS-RD16/0011/0011, PIE15/00048, PI18-01379), and Dirección General de Investigación de la Comunidad de Madrid (AvanCell-CM; Ref S2017/BMD-3692

Comparative analysis of the immunomodulatory capacities of human bone marrow– and adipose tissue–derived mesenchymal stromal cells from the same donor

Background aims The immunomodulatory properties of mesenchymal stromal cells (MSCs), together with their tissue regenerative potential, make them interesting candidates for clinical application. Methods In the current study, we analyzed the in vitro immunomodulatory effects of MSCs derived from bone marrow (BM-MSCs) and from adipose tissue (AT-MSCs) obtained from the same donor on both innate and acquired immunity cells. BM-MSCs and AT-MSCs were expanded to fourth or fifth passage and co-cultured with T cells, monocytes or natural killer (NK) cells isolated from human peripheral blood and stimulated in vitro. The possible differing impact of MSCs obtained from distinct sources on phenotype, cell proliferation and differentiation, cytokine production and function of these immune cells was comparatively analyzed. Results BM-MSCs and AT-MSCs induced a similar decrease in NK-cell proliferation, cytokine secretion and expression of both activating receptors and cytotoxic molecules. However, only BM-MSCs significantly reduced NK-cell cytotoxic activity, although both MSC populations showed the same susceptibility to NK-cell-mediated lysis. AT-MSCs were more potent in inhibiting dendritic-cell (DC) differentiation than BM-MSC, but both MSC populations similarly reduced the ability of DCs to induce CD4+ T-cell proliferation and cytokine production. BM-MSCs and AT-MSCs induced a similar decrease in T-cell proliferation and production of inflammatory cytokines after activation. Conclusions AT-MSCs and BM-MSCs from the same donor had similar immunomodulatory capacity on both innate and acquired immunity cells. Thus, other variables, such as accessibility of samples or the frequency of MSCs in the tissue should be considered to select the source of MSC for cell therapy