Implementation of palliative care as a mandatory cross-disciplinary subject (QB13) at the Medical Faculty of the Heinrich-Heine-University Düsseldorf, Germany.

Background: By means of the revision of the Medical Licensure Act for Physicians (ÄAppO) in 2009, undergraduate palliative care education (UPCE) was incorporated as a mandatory cross sectional examination subject (QB13) in medical education in Germany. Its implementation still constitutes a major challenge for German medical faculties. There is a discrepancy between limited university resources and limited patient availabilities and high numbers of medical students.

Significant clinical, neuropathological and behavioural recovery from acute spinal cord trauma by transplantation of a well-defined somatic stem cell from human umbilical cord blood.

Stem cell therapy is a potential treatment for spinal cord injury and different stem cell types have been grafted into animal models and humans suffering from spinal trauma. Due to inconsistent results, it is still an important and clinically relevant question which stem cell type will prove to be therapeutically effective. Thus far, stem cells of human sources grafted into spinal cord mostly included barely defined heterogeneous mesenchymal stem cell populations derived from bone marrow or umbilical cord blood.

Lentiviral labeling reveals three germ layer differentiation potential of a single unrestricted somatic stem cell from human cord blood.

Objective: Generation and expression of unrestricted somatic stem cells (USSC) from human cord blood as well as their in vitro functional characterization at the clonal level.

Materials And Methods: USSC generation was initiated from fresh cord blood followed by lentiviral transfection and clone generation via limiting dilution. Individual clones were analyzed for lentiviral genomic integration patterns by ligation-mediated polymerase chain reaction.

Hepatocyte growth factor-mediated attraction of mesenchymal stem cells for apoptotic neuronal and cardiomyocytic cells.

Human bone marrow-derived mesenchymal stem cells (MSC) home to injured tissues and have regenerative capacity. In this study, we have investigated in vitro the influence of apoptotic and necrotic cell death, thus distinct types of tissue damage, on MSC migration. Concordant with an increased overall motility, MSC migrated towards apoptotic, but not vital or necrotic neuronal and cardiac cells.

Hepatocyte growth factor/c-MET axis-mediated tropism of cord blood-derived unrestricted somatic stem cells for neuronal injury.

An under-agarose chemotaxis assay was used to investigate whether unrestricted somatic stem cells (USSC) that were recently characterized in human cord blood are attracted by neuronal injury in vitro. USSC migrated toward extracts of post-ischemic brain tissue of mice in which stroke had been induced. Moreover, apoptotic neurons secrete factors that strongly attracted USSC, whereas necrotic and healthy neurons did not.

Trauma-associated inflammatory response impairs embryonic stem cell survival and integration after implantation into injured rat brain.

Pluripotent embryonic stem cells were shown to survive and differentiate into mature neuronal cells after implantation in experimental models of Parkinson disease and cerebral ischemia. Embryonic stem cell transplantation has also been proposed as a potential therapy for cerebral trauma, characteristic of massive loss of multiple cell types due to primary insult and secondary sequelae. Green fluorescent protein (GFP)-transfected murine embryonic stem cells were implanted into the ipsi or contralateral cortex of male Sprague-Dawley rats 72 h after fluid-percussion injury.

Proteomics of experimental stroke in mice.

Multi-Western blots of more than 400 proteins were performed from brain extracts of mice submitted to transient focal ischemia induced by 1 h middle cerebral artery (MCA) thread occlusion. Measurements were carried out in groups of six animals in sham-operated controls, at the end of 1 h ischemia, and after 3 and 12 h recirculation. After MCA occlusion up to 45% of proteins were up- or downregulated in the ipsilateral hemisphere by a factor of 1.

Caffeine-mediated enhancement of glucocorticoid receptor activity in human osteoblastic cells.

Caffeine-containing beverage consumption has been reported to be associated with an increased risk for osteoporosis. Since the glucocorticoid receptor (GR) is a major factor in the induction of osteoporosis we analyzed whether caffeine may act via altering GR function. Applying a reporter gene assay we provide evidence that caffeine drastically amplifies GR transcriptional activity in human osteoblastic cells.

[Embryonic stem cell therapy in experimental stroke: host-dependent malignant transformation].

Introduction: Therapeutic application of embryonic stem cells in neurodegenerative disorders like stroke is widely investigated in preclinical animal models.

Aim: The authors studied the therapeutic potential of murine embryonic stem cells in two rodent models of stroke.

Methods: Undifferentiated and predifferentiated stem cells were implanted into the non-ischemic hemisphere of mice and rats following focal brain ischemia.

A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential.

Here a new, intrinsically pluripotent, CD45-negative population from human cord blood, termed unrestricted somatic stem cells (USSCs) is described. This rare population grows adherently and can be expanded to 10(15) cells without losing pluripotency. In vitro USSCs showed homogeneous differentiation into osteoblasts, chondroblasts, adipocytes, and hematopoietic and neural cells including astrocytes and neurons that express neurofilament, sodium channel protein, and various neurotransmitter phenotypes.

Immunohistochemical analysis of protein expression after middle cerebral artery occlusion in mice.

The effect of transient focal cerebral ischemia on protein regulation was studied in mice using multiparametric immunohistochemistry. Injury was characterized by measurements of blood flow, regional protein synthesis and terminal transferase biotinylated-dUTP nick end labeling (TUNEL). The proteins studied were selected from a previously established list of differentially regulated proteins and included the GTPases dynamin, RhoB, CAS and Ran BP-1, the transcription factors Nurr1 and p-Stat 6, the protein kinase MAPK p49, the splicing factors SRPK1 and hPrp16, the cell cycle control proteins cyclin B1 and Nek2, the inflammatory proteins FKBP12 and Rag2, the cell adhesion protein paxillin and the folding protein TCP-1.

Host-dependent tumorigenesis of embryonic stem cell transplantation in experimental stroke.

The therapeutical potential of transplantation of undifferentiated and predifferentiated murine embryonic stem cells for the regeneration of the injured brain was investigated in two rodent stroke models. Undifferentiated embryonic stem cells xenotransplanted into the rat brain at the hemisphere opposite to the ischemic injury migrated along the corpus callosum towards the damaged tissue and differentiated into neurons in the border zone of the lesion. In the homologous mouse brain, the same murine embryonic stem cells did not migrate, but produced highly malignant teratocarcinomas at the site of implantation, independent of whether they were predifferentiated in vitro to neural progenitor cells.

Transgenic mice overexpressing XIAP in neurons show better outcome after transient cerebral ischemia.

X-chromosome linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitor of apoptosis protein (IAP) family and known to inhibit death of various cells under different experimental conditions. Although present in brain tissue, little is known about the physiology of the IAPs in nerve cells. Here we report on the establishment of transgenic mice with overexpression of human XIAP in brain neurons.

Chronic glucocorticoid receptor activation impairs CREB transcriptional activity in clonal neurons.

Excessive circulating levels of glucocorticoids are thought to be associated with cognitive impairment. We provide evidence that chronic activation of the glucocorticoid receptor (GR) in clonal neurons inhibits the transcriptional activity of the cyclic AMP response element-binding protein (CREB), which is believed to be involved in memory processes. To investigate the underlying mechanism we studied the phosphorylation of CREB and found altered phosphorylation kinetics in neurons chronically treated with glucocorticoids.

Monitoring of implanted stem cell migration in vivo: a highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat.

In vivo monitoring of stem cells after grafting is essential for a better understanding of their migrational dynamics and differentiation processes and of their regeneration potential. Migration of endogenous or grafted stem cells and neurons has been described in vertebrate brain, both under normal conditions from the subventricular zone along the rostral migratory stream and under pathophysiological conditions, such as degeneration or focal cerebral ischemia. Those studies, however, relied on invasive analysis of brain sections in combination with appropriate staining techniques.