Histology and histopathology Vol.32,nº10 (2017)
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- PublicationOpen AccessSeven days post-injury fate and effects of genetically labelled adipose-derived mesenchymal cells on a rat traumatic brain injury experimental model(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Dori, Ioanna; Petrakis, Spyros; Giannakopoulou, Aggeliki; Bekiari, Chryssa; Grivas, Ioannis; Siska, Evangelia K.; Koliakos, Georgios; Papadopoulos, Georgios C.Mesenchymal stromal cells (MSC) have been suggested to have beneficial effects on animal models of traumatic brain injury (TBI), owing to their neurotrophic and immunomodulatory properties. Adipose tissuederived stromal cells (ASCs) are multipotent MSC that can be harvested with minimally invasive methods, show a high proliferative capacity, low immunogenicity if allogeneic, and can be used in autologous or heterologous settings. In the present study ASCs were genetically labelled using the Sleeping Beauty transposon to express the fluorescent protein Venus. Venus+ASCs were transplanted intra-cerebroventricularly (ICV), on a rat TBI model and their survival, fate and effects on host brain responses were examined at seven days post-injury (7dPI). We provide evidence that Venus+ASCs survived, migrated into the periventricular striatum and were negative for neuronal or glial lineage differentiation markers. Venus+ASCs stimulated the proliferation of endogenous neural stem cells (NSCs) in the brain neurogenic niches, the subventricular zone (SVZ) and the hippocampal dentate gyrus (DG). It was also evident that Venus+ASCs modify the host brain’s cellular microenvironment both at the injury site and at their localization area by promoting a significant reduction of the lesion area, as well as altering the post-injury, pro-inflammatory profile of microglial and astrocytic cell populations. Our data support the view that ICV transplantation of ASCs induces alterations in the host brain’s cellular response to injury that may be correlated to a reversal from a detrimental to a beneficial state which is permissive for regeneration and repair.
- PublicationOpen AccessTargeting exogenous β-Defensin to the endolysosomal compartment via a vehicle guided system(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Carvelli, Lorena; Libin, Yuan; Esfandnia, Sherry; Zhang, Yan; Presley, John F.; Morales, Carlos R.A number of pathogens for which there are no effective treatments infect the cells via endocytosis. Once in the endosomes, the pathogens complete their life cycle by overriding normal lysosomal functions. Recently, our laboratory identified the lysosomal targeting signal of prosaposin, which is recognized by the sorting receptor “sortilin”. Based on this evidence, we tested whether the antimicrobial peptide β-Defensin linked to the targeting sequence of prosaposin (βDPSAP) could be redirected from its secretory pathway to the endolysosomal compartment. To this effect, βDPSAP was transfected into COS-7 cells. The sub-cellular distribution of βD-PSAP was analyzed by confocal microscopy and differential centrifugation. Confocal microscopy demonstrated that βD-PSAP overlaid with the lysosomal marker LAMP1, indicating that the construct reached endosomes and lysosomes. Differential centrifugation also showed that βD-PSAP was in the lysosomal fractions. In addition, our binding inhibition assay demonstrated that βD-PSAP bound specifically to sortilin. Similarly, the delivery of βDPSAP was abolished after overexpressing a truncated sortilin. These results indicate that the prosaposin Cterminus and D/C-domain (prosaposin targeting sequence) was an effective “guidance system” to redirect βD-PSAP to the endolysosomal compartment. In the future, this and other fusion proteins with antimicrobial properties will be assembled to our “biotic vehicle” to target pathogens growing within these compartments.
- PublicationOpen AccessGLUT1, MCT1/4 and CD147 overexpression supports the metabolic reprogramming in papillary renal cell carcinoma(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Almeida, L.M.C.A.; Silva, R.; Cavadas, B.; Lima, J.; Pereira, L.; Soares, P.; Sobrinho Simões, M.; Lopes, J.M.; Máximo, V.Papillary Renal Cell carcinoma (pRCC) is the second most common type of RCC, accounting for about 15% of all RCCs. Surgical excision is the main treatment option. Still, 10-15 % of clinically localized tumours will recur and/or develop metastasis early after surgery, and no reliable prognostic biomarkers are available to identify them. It is known that pRCC cells rely on high rates of aerobic glycolysis, characterized by the up-regulation of many proteins and enzymes related with the glycolytic pathway. However, a metabolic signature enabling the identification of advanced pRCC tumours remains to be discovered. The aim of this study was to characterize the metabolic phenotype of pRCCs (subtypes 1-pRCC1 and 2-pRCC2) by evaluating the expression pattern of the glucose transporters (GLUTs) 1 and 4 and the monocarboxylate transporters (MCTs) 1 and 4, as well as their chaperon CD147. We analysed the clinicopathological data and the protein and mRNA expression of GLUT1, GLUT4 and MCT1, MCT4 and CD147 in tumours from Porto and TCGA series (http://cancer genome.nih.gov/), respectively. With the exception of GLUT4, plasma membrane expression of all proteins was frequently observed in pRCCs. GLUT1 and MCT1 membrane overexpression was significantly higher in pRCC2 and significantly associated with higher pN-stage and higher Fuhrman grade. Overexpression of GLUT1, MCT1/4 and CD147, supports the metabolic reprograming in pRCCs. MCT1 expression was associated with pRCC aggressiveness, regardless of the tumour histotype.
- PublicationOpen AccessDetection of PR-39, a porcine host defence peptide, in different cell sub-linages in pigs infected with Actinobacillus pleuropneumoniae(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Gabner, S.; Egerbacher, M.; Gasse, H.; Hewicker Trautwein, M.; Höltig, D.; Waldmann, K. H.; Blecha, F.; Saalmüller, A.; Hennig Pauka, I.Innate immunity is critically important for the outcome of infection in many diseases. It was previously shown that cathelicidin PR-39, an important porcine multifunctional host defence peptide, is elevated in bronchoalveolar lavage fluid and respiratory tract tissue after experimental infection with Actinobacillus pleuropneumoniae (A.pp.). To date, neutrophil polymorphonuclear leukocytes (PMNs) are thought to be the only source of PR-39. The aim of this study was to further characterize PR39+ cells and selected immune cell populations in lung tissue during the peracute (7-10 hours), acute (2 days), reconvalescent (7 days) and chronic (21 days) stages of experimental infection with A.pp. serotype 2. In total, six mock-infected control pigs and 12 infected pigs were examined. Using immunofluorescence double-labeling, antibodies against PR-39 were combined with antibodies against CD3 (T-cells), CD79 (B-cells), Iba1 (activated macrophages), TTF-1 (lung epithelial cells expressing surfactant proteins), macrophage/L1 protein and myeloperoxidase (MPO, cells of the myeloid linage). In the peracute and acute phases of infection, total PR-39+ cells and myeloid linage cells increased, whereas CD3+ cells and TTF-1+ cells decreased. Double labeling revealed that most Macrophage/L1 protein+ cells and to a lesser extent MPO+ cells co-expressed PR-39. In addition, few bronchial epithelial cells and type 2 alveolar epithelial cells (both identified with TTF-1) produced PR-39. Occasionally, CD3+ T cells expressing PR-39 were seen in infected animals. Taken together, this study identifies cell types, other than PMNs, in lungs of A.pp.-infected pigs that are capable of producing PR-39. In addition, these findings provide further insights into the dynamics of different immune cell populations during A.pp.-infection.
- PublicationOpen AccessOvarian Leydig cells (OLC): A histomorphological and immunohistochemical study(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Carrasco Juan, J.L.; Álvarez Argüelles Cabrera, H.; Martín Corriente, M.C.; González Gómez, M.; Valladares Parrilla, F.; Gutiérrez García, R.; Díaz Flores, L.Testicular Leydig cells (LC) regulate the proper development of male individuals, both during fetal life (fetal LC) and puberty (adult LC). In the ovaries of adult women, there are cells that are very similar to Leydig cells, the ovarian hilus cells (OHC), which also produce testosterone. The origin of these cells, in both sexes, remains unknown and is still a matter of debate. We have studied the location, characteristics and relationships of the OHC in 90 patients. The indications for oophorectomy were: metrorrhagia (n=9), prolapse (n=8), endometrial hyperplasia (n=14), cancer (endometrial, myometrial, or cervical) (n=35), uterine leiomyomata (n=14), and various ovarian tumors (cysts and benign tumors, borderline and malignant) (n=10). In addition to the hilus, occasionally the nodules, nests and clusters of OHC were located in the mesovarium, the mesosalpinx, and in the medullar and cortical regions of the ovaries. The morphological (including crystalloids of Reinke) and immunohistochemical (positivity for calretinin and alpha-inhibin) findings were similar to those described for testicular LC. Therefore, OHC can be considered ovarian Leydig cells (OLC). LC are usually found in small numbers in the ovaries, but if one looks for them intentionally, one always finds them. Close relationships were observed between the OLC with nerves and vessels. Moreover, an intraneural location of the OLC was demonstrated in all cases, and these intraneural cells showed similar characteristics to extraneural OLC, suggesting that they derive from endoneural cells which are present in the vegetative nerves of the ovaries.