Jürgen Hescheler

University of Cologne, Köln, North Rhine-Westphalia, Germany

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Publications (473)2089.91 Total impact

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    ABSTRACT: Recently, growing attention has been directed toward stem cell metabolism, with the key observation that the plasticity of stem cells also reflects the plasticity of their energy substrate metabolism. There seems to be a clear link between the self-renewal state of stem cells, in which cells proliferate without differentiation, and the activity of specific metabolic pathways. Differentiation is accompanied by a shift from anaerobic glycolysis to mitochondrial respiration. This metabolic switch of differentiating stem cells is required to cover the energy demands of the different organ-specific cell types. Among other metabolic signatures, amino acid and carbohydrate metabolism is most prominent in undifferentiated embryonic stem cells, whereas the fatty acid metabolic signature is unique in cardiomyocytes derived from embryonic stem cells. Identifying the specific metabolic pathways involved in pluripotency and differentiation is critical for further progress in the field of developmental biology and regenerative medicine. The recently generated knowledge on metabolic key processes may help to generate mature stem cell-derived somatic cells for therapeutic applications without the requirement of genetic manipulation. In the present review, the literature about metabolic features of stem cells and their cardiovascular cell derivatives as well as the specific metabolic gene signatures differentiating between stem and differentiated cells are summarized and discussed.
    Circulation Research 04/2014; 114(8):1346-60. · 11.86 Impact Factor
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    ABSTRACT: It is debatable whether a local inflammatory tissue response caused by herniated disc material contributes to sciatic pain and/or sensorimotor deficits. The impact of inflammatory changes on local tissue remodelling, the healing process and the clinical course of disease remains unclear. In this prospective observational study, we included a total of 31 patients with a single-level, unilateral lumbar disc herniation. The diagnosis was confirmed by magnetic resonance imaging (MRI)±gadolinium. The presence of peridiscal contrast enhancement was correlated with the extent of inflammatory reactions in the herniated fragments as confirmed by immunohistochemistry; clinical symptoms, including the duration of radicular pain; and the incidence of sensorimotor deficits. Peridiscal contrast enhancement was found in 17 patients (55%) and was encasing the adjacent rootlet in 4 cases. There was no significant correlation between gadolinium uptake and the presence of sensorimotor deficits or the duration of radicular symptoms. Degenerative changes were observed in all 31 disc specimens. Overall, 18 cases exhibited increased cellularity in the marginal areas, which were mostly populated by CD68(+) macrophages and fibroblasts. Additionally, these areas displayed a limited number of CD3(+) T-lymphocytes and different degrees of concomitant neovascularisation, which represented a chronic and unspecific immune response. Peridiscal contrast enhancement on MRI was significantly correlated with the histopathological characteristics of tissue inflammation. However, no correlation was found between the histological evidence and the degree of inflammation and neurological symptoms. Gadolinium-enhanced MRI is a sensitive method to detect unspecific inflammatory reactions in therapy-naïve disc herniations. However, the neuroradiological and histological evidence of peridiscal inflammation was not correlated with the severity of pain or sensorimotor deficits in our patients. Additional research is needed because the occurrence of local inflammation may indicate an ongoing degradation of herniated fragments and thus be helpful in therapeutic decision-making.
    Clinical neurology and neurosurgery 04/2014; 119:28-34. · 1.30 Impact Factor
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    ABSTRACT: Intracellular Mg<sup>2+</sup> which is implicated in arrhythmogenesis and transient cardiac ischemia, inhibits L-type Ca<sup>2+</sup> channels current ( I <sub>CaL</sub>) of adult cardiomyocytes. We take the advantage of an in vitro model of cardiomyocytes based on induced pluripotent stem (iPS) cells to investigate the effects of intracellular Mg<sup>2+</sup> on the phosphorylation or dephosphorylation processes of L-type Ca<sup>2+</sup> channel (LTCCs) at early and late stages of cardiac cell differentiation. Using the whole-cell patch-clamp technique, we demonstrate that increasing intracellular Mg<sup>2+</sup> concentration [Mg<sup>2+</sup>]<sub>i</sub> from 0.2 mmol/L to 5 mmol/L markedly reduced the peak of I <sub>CaL</sub> density, showing less effect on both the activation and inactivation properties in the late developmental stage (LDS) of CMs differentiation more so than in the early developmental stage (EDS). Raising the [Mg<sup>2+</sup>]<sub>i</sub> from 0.2 mmol/L to 2 mmol/L in the presence of cAMP-dependent protein kinase A (PKA) significantly decreased I <sub>CaL</sub> in LDS (70%) and in EDS (36%) CMs. In addition, the effect of forskolin was greatly attenuated in the presence of 2 mmol/L [Mg<sup>2+</sup>]<sub>i</sub> in LDS but not in EDS cardiomyocytes. The effect of forskolin was enhanced in the presence of ATP-γ-S in LDS cardiomyocytes compared with EDS cardiomyocytes. The exposure of both EDS and LDS cardiomyocytes to 2 mmol/L [Mg<sup>2+</sup>]<sub>i</sub> considerably reduced the effects of isobutylmethylxanthine (IBMX) and okadaic acid (OA) on I <sub>CaL</sub>. Our results provide evidence for differential regulation of LTCCs activities by cytosolic Mg<sup>2+</sup> concentration in developing cardiac cells and confirm that Mg<sup>2+</sup> acts under conditions that favor opening of the LTCCs caused by channel phosphorylation.
    Stem cells and development 02/2014; · 4.15 Impact Factor
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    International journal of cardiology 01/2014; · 7.08 Impact Factor
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    ABSTRACT: Information on design principles governing transcriptome changes upon transition from safe to hazardous drug concentrations or from tolerated to cytotoxic drug levels are important for the application of toxicogenomics data in developmental toxicology. Here, we tested the effect of eight concentrations of valproic acid (VPA; 25-1000 μM) in an assay that recapitulates the development of human embryonic stem cells to neuroectoderm. Cells were exposed to the drug during the entire differentiation process, and the number of differentially-regulated genes increased continuously over the concentration range from zero to about 3000. We identified overrepresented transcription factor binding sites (TFBS) as well as superordinate cell biological processes, and we developed a 'gene ontology (GO) activation profiler', as well as a two-dimensional 'teratogenicity index'. Analysis of the transcriptome data set by the above biostatistical and systems biology approaches yielded following insights: (i) 'tolerated' (≤25 μM), 'deregulated/teratogenic' (150 - 550 μM) and 'cytotoxic' (≥800 μM) concentrations could be differentiated. (ii) Biological signatures related to the mode of action of VPA, such as protein acetylation, developmental changes, and cell migration emerged from the teratogenic concentrations range. (iv) Cytotoxicity was not accompanied by signatures of newly-emerging canonical cell death/stress indicators, but by catabolism and decreased expression of cell cycle associated genes. (v) Most, but not all of the GO groups and TFBS seen at the highest concentrations were already overrepresented at 350 - 450 μM. (vi) The 'teratogenicity index' reflected this behavior, and thus differed strongly from cytotoxicity. Our findings suggest the use of the highest non-cytotoxic drug concentration for gene array toxicogenomics studies, as higher concentrations possibly yield wrong information on the mode-of action, and lower drug levels result in decreased gene expression changes and thus a reduced power of the study.
    Chemical Research in Toxicology 01/2014; · 3.67 Impact Factor
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    ABSTRACT: Rationale Pathologic ECG events are known to accompany seizures and to persist in several chronic epilepsy syndromes. The contribution of antiepileptic drugs (AEDs) to these events and the implications in the etiology of sudden-unexpected death in epilepsy (SUDEP) continue to be a matter of debate. We therefore investigated cardiac parameters during kainic-acid (KA) induced experimental epilepsy and antiepileptic treatment with lamotrigine (LTG). Methods Epilepsy was induced in seven C57Bl/6 mice by injections of KA (20 mg/kg) on days 1 and 5, which produced severe acute seizures and spontaneous seizures 10 days later. Treatment with LTG (30 mg/kg) was initiated on day 11 and repeated on day 12. Continuous ECGs and ECoGs were collected telemetrically from freely moving mice. Results Mice displayed pre-ictal but not ictal tachycardia. The squared coefficient of variation (SCV) of R-R intervals was significantly elevated 30 seconds before and during seizures compared to control conditions. LTG produced a significant reversible increase in SCV and LF/HF ratio during slow-wave sleep (SWS), potentially indicative of sympatho-vagal imbalance during this state of vigilance, in which epileptic patients are known to be particularly vulnerable to SUDEP. Significance The KA model used in this study permits the investigation of cardiac phenomena during epilepsy, as it features many effects found in human epileptic patients. Increased LF/HF, a known risk factor for cardiac disease, which is often found in epileptic patients, was observed as a side-effect of LTG treatment during SWS, suggesting that LTG may promote imbalance of the autonomous nervous system in epileptic mice.
    Epilepsy research 01/2014; · 2.48 Impact Factor
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    ABSTRACT: Induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) might become therapeutically relevant to regenerate myocardial damage. Purified iPS-CMs exhibit poor functional integration into myocardial tissue. The aim of this study was to investigate whether murine mesenchymal stem cells (MSCs) or their conditioned medium (MScond) improve the integration of murine iPS-CMs into myocardial tissue. Vital or non-vital embryonic murine ventricular tissue slices were co-cultured with purified clusters of iPS-CMs in combination with either murine embryonic fibroblasts (MEFs), MSCs or MScond. Morphological integration was assessed by visual scoring and functional integration by isometric force and field potential measurements. We observed a moderate morphological integration of iPS-CM clusters into vital, but a poor integration into non-vital, slices. MEFs and MSCs but not MScond improved morphological integration of CMs into non-vital slices and enabled purified iPS-CMs to confer force. Co-culture of vital slices with iPS-CMs and MEFs or MSCs resulted in an improved electrical integration. A comparable improvement of electrical coupling was achieved with the cell-free MScond, indicating that soluble factors secreted by MSCs were involved in electrical coupling. We conclude that cells such as MSCs support the engraftment and adhesion of CMs, and confer force to non-contractile tissue. Further- more, soluble factors secreted by MSCs mediate electrical coupling of purified iPS-CM clusters to myocardial tissue. These data suggest that MSCs may increase the functional engraftment and therapeutic efficacy of transplanted iPS-CMs into infarcted myocardium.
    Stem cells and development 11/2013; · 4.15 Impact Factor
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    Archives of Toxicology 11/2013; · 5.22 Impact Factor
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    ABSTRACT: Aims: It is important to screen and identify chemical compounds to improve the efficiency of cardiac differentiation and specialization of embryonic stem (ES) cells. The objective of this study was to investigate the effect of puerarin, a natural phytoestrogen, on the in vitro cardiac differentiation and ventricular specialization of murine ES cells. Methods: Cardiac differentiation of murine ES cells was performed by embryoid body (EB)-based differentiation method. Quantitative RT-PCR, flow cytometry and immunofluorescence were employed to identify cardiomyocytes (CMs) derived from murine ES cells (mES-CMs). Patch clamp was used to study the electrophysiological properties of CMs. Results: We found that continuous puerarin treatment significantly increased the population of ES-CMs which express typical cardiac markers and are electrophysiological intact. Puerarin treatment shifted the cardiac phenotype from pacemaker-like cells to ventricular-like cells, which were Mlc2v-positive and present typical ventricular-like AP. Puerarin up-regulated transcripts involved in cardiac differentiation and ventricular specialization of ES cells. Conclusion: Our results suggest that puerarin promotes cardiac differentiation, and significantly enhances the specialization of mES cells into ventricular-like CMs. Puerarin may be used to increase the yield of ventricular mES-CMs during in vitro differentiation. © 2013 S. Karger AG, Basel.
    Cellular Physiology and Biochemistry 09/2013; 32(4):789-800. · 3.42 Impact Factor
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    ABSTRACT: Induced pluripotent stem cell-derived cardiomyocytes (iPSCM) are regarded as promising cell type for cardiac cell replacement therapy. We investigated long-term electrophysiological integration and maturation of transplanted iPSCM, which are essential for therapeutic benefit.Methods and ResultsMurine iPSCM expressing eGFP and a puromycin resistance under control of the α-MHC promoter were purified by antibiotic selection and injected into adult mouse hearts. After 6-12 days, 3-6 weeks or 6-8 months, viable slices of recipient hearts were prepared. Slices were focally stimulated by a unipolar electrode placed in host tissue, and intracellular action potentials (APs) were recorded with glass microelectrodes in transplanted cells and neighboring host tissue within the slices.Persistence and electrical integration of transplanted iPSCM into recipient hearts could be demonstrated at all time-points. Quality of coupling improved, as indicated by a maximal stimulation frequency without conduction blocks of 5.77±0.54 Hz at 6-12 days, 8.98±0.38 Hz at 3-6 weeks and 10.82±1.07 Hz at 6-8 months after transplantation. AP properties of iPSCM became more mature from 6-12 days to 6-8 months after transplantation, but still differed significantly from those of host APs. Transplanted iPSCM can persist in the long term and integrate electrically into host tissue, supporting their potential for cell replacement therapy. Quality of electrical integration improves between 6-12 days and 6-8 months after transplantation, and there are signs of an electrophysiological maturation. However, even after 6-8 months, AP properties of transplanted iPSCM differ from those of recipient cardiomyocytes.
    Cardiovascular research 09/2013; · 5.80 Impact Factor
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    ABSTRACT: Pluripotent stem cells have great potential for regenerative medicine; however, their clinical use is associated with a risk of tumor formation. We utilized pluripotent cells expressing green fluorescent protein and puromycin resistance under control of the Oct4 promoter to study the persistence of potential pluripotent cells under embryoid body (EB) culture conditions, which are commonly used to obtain organotypic cells. We found that i.) OCT4-expressing cells dramatically decrease during the first week of differentiation, ii.) the number of OCT4-expressing cells recovers from day 7 on, iii.) the OCT4-expressing cells are similar to embryonic stem cells grown in the presence of leukemia inhibitory factor LIF but express several markers associated with germ cell formation, such as DAZL and STRA-8 and iv.) the persistence of potentially pluripotent cells is independent of supportive cells in EBs. Finally, OCT4-expressing cells, isolated from EBs after 2-month of culture, were further maintained under feeder-free conditions in absence of LIF and continued to express OCT4 in 95 % of the population for at least 36 days. These findings point to an alternative state of stable OCT4 expression. In the frame of the landscape model of differentiation two attractors of pluripotency might be defined based on their different characteristics.
    Stem cell reviews 09/2013; · 5.08 Impact Factor
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    ABSTRACT: Background/Aims: Low efficiency of cardiomyocyte (CM) differentiation from embryonic stem (ES) cells limits their therapeutic use. The objective of this study was to investigate the effect of baicalin, a natural flavonoid compound, on the in vitro cardiac differentiation of murine ES cells. Methods: The induction of ES cells into cardiac-like cells was performed by embryoid body (EB)-based differentiation method. The electrophysiological properties of the ES cell-derived CMs (ES-CMs) were measured by patch-clamp. The biomarkers of ES-CMs were determined by quantitative RT-PCR and immunofluorescence. Results: Continuous baicalin treatment decreased the size of EBs, and increased the proportion of α-actinin-positive CMs and transcript level of cardiac specific markers in beating EBs by inducing cell death of non-CMs. Baicalin increased the percentage of working ES-CMs which had typical responses to β-adrenergic and muscarinic stimulations. Conclusion: Baicalin maintains the late-stage functional CMs in EBs derived from murine ES cells. This study describes a new insight into the various biological effects of baicalin on cardiac differentiation of pluripotent stem cells.
    Cellular Physiology and Biochemistry 07/2013; 32(1):86-99. · 3.42 Impact Factor
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    ABSTRACT: Background: The first electrocardiograms (ECGs) have been recorded with a capillary electrometer in the late 19(th) century by John Burdon Sanderson and Augustus Waller. In 1903 Willem Einthoven used the much more sensitive string galvanometer and was awarded Nobel Price in Medicine for this discovery. Though the physical principles of that era are still in use, there have been many advances but also challenges in cardiac electrophysiology over the last decades. One challenge is to record electrocardiograms of rather small animals such as mice and even smaller organisms such as their embryos. As mice belong to the most routinely used laboratory animals it is important to better understand their physiology and specific diseases. We therefore aimed to study whether it is feasible to measure electrical activities of embryonic mouse hearts. Methods and Results: For our studies we used substrate-integrated Microelectrode Arrays combined with newly developed stimulation electrodes to perform electrophysiological studies in these hearts. The system enabled us to perform ECG-like recordings with atrio-ventricular (anterograde) and ventriculo-atrial (retrograde) stimulation. The functional separation of atria and ventricles, indicated by a stable atrio-ventricular conduction time, occurred clearly earlier than the morphological separation. Electrical stimulation induced a reversible prolongation of the anterograde and retrograde conduction up to atrio-ventricular conduction blocks at higher frequencies. Conclusion: These results yield new insight into functional aspects of murine cardiac development, and may help as a new diagnostic tool to uncover the functional and electrophysiological background of embryonic cardiac phenotypes of genetically altered mice.
    Cellular Physiology and Biochemistry 07/2013; 32(1):1-10. · 3.42 Impact Factor
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    ABSTRACT: Background: Stem cell therapy has been proposed as a potential treatment strategy for ischemic cardiomyopathy in recent years. A variety of stem cells or stem cell-derived cells can potentially be used for transplantation. Despite improved cardiac function after treatment, one of the major problems is the poor integration between host and donor cells which can lead to post-transplantation arrhythmia and poor long-term outcome. Methods: In the present study, we cocultured murine embryonic stem cells (mES) with murine embryonic ventricular myocytes (mEVs) in hanging drops to assess the cellular interaction and function of mES-derived cardiomyocytes under these conditions. Results: We found that when mEVs are added to a culture system of embryonic stem cells, the number of spontaneously beating areas in embryoid bodies (EBs) increases, intercellular gap junction communication is enhanced by upregulation of Cx43 expression at the mid-developmental stage and Cx43 is distributed more orderly between cardiomyocytes. Conclusions: Our findings suggest mES-derived cardiomyocytes are able to form effective signaling pathways through coculture with mEVs which is important for providing more functional grafts for cardiac cell therapy by improving the integration between transplanted and host cells.
    Cellular Physiology and Biochemistry 07/2013; 32(1):53-63. · 3.42 Impact Factor
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    ABSTRACT: PURPOSE: Lamotrigine (LTG) is a popular modern antiepileptic drug (AED); however, its mechanism of action has yet to be fully understood, as it is known to modulate many members of several ion channel families. In heterologous systems, LTG inhibits Cav 2.3 (R-type) calcium currents, which contribute to kainic-acid (KA)-induced epilepsy in vivo. To gain insight into the role of R-type currents in LTG drug action in vivo, we compared the effects of LTG to two other AEDs in Cav 2.3-deficient mice and controls on KA-induced seizures. METHODS: Behavioral seizure rating and quantitative electrocorticography were performed after injection of 20 mg/kg (and 30 mg/kg) KA. One hour before KA injection, mice were pretreated with 30 mg/kg LTG, 50 mg/kg topiramate (TPM), or 30 mg/kg lacosamide (LSM). KEY FINDINGS: Ablation of Cav 2.3 reduced total seizure scores by 28.6% (p = 0.0012), and pretreatment with LTG reduced seizure activity of control mice by 23.2% (p = 0.02). In Cav 2.3-deficient mice, LTG pretreatment increased seizure activity by 22.1% (p = 0.018) and increased the percentage of degenerated CA1 pyramidal neurons (p = 0.02). All three AEDs reduced seizure activity in control mice; however, only the non-calcium channel modulating AED, LSM, had an anticonvulsive effect in Cav 2.3-deficient mice. Furthermore, LTG altered electrocorticographic parameters differently in the two genotypes: decreasing relative power of ictal spikes in control mice but increasing relative power of high frequency fast ripple discharges during seizures in Cav 2.3-deficient mice. SIGNIFICANCE: These findings provided the first in vivo evidence for an essential role for Cav 2.3 in LTG pharmacology and shed light on a paradoxical effect of LTG in their absence. Furthermore, LTG appears to promote ictal activity in Cav 2.3-deficient mice by increasing high frequency components of seizures, resulting in increased neurotoxicity in the CA1. This paradoxical mechanism, possibly reflecting rebound hyperexcitation of pyramidal CA1 neurons after increased inhibition, may be key in understanding LTG-induced seizure aggravation observed in clinical practice.
    Epilepsia 06/2013; · 3.96 Impact Factor
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    ABSTRACT: Derivation of cardiomyocytes from induced pluripotent stem cells (iPS-CMs) allowed us to probe the Ca(2+)-signaling parameters of human iPS-CMs from healthy- and catecholaminergic polymorphic ventricular tachycardia (CPVT1)-afflicted individuals carrying a novel point mutation p.F2483I in ryanodine receptors (RyR2). iPS-CMs were dissociated on day 30-40 of differentiation and patch-clamped within 3-6 days. Calcium currents (ICa) averaged ~8pA/pF in control and mutant iPS-CMs. ICa-induced Ca(2+)-transients in control and mutant cells had bell-shaped voltage-dependence similar to that of ICa, consistent with Ca(2+)-induced Ca(2+)-release (CICR) mechanism. The ratio of ICa-activated to caffeine-triggered Ca(2+)-transients was ~0.3 in both cell types. Caffeine-induced Ca(2+)-transients generated significantly smaller Na(+)-Ca(2+) exchanger current (INCX) in mutant cells, reflecting their smaller Ca(2+)-stores. The gain of CICR was voltage-dependent as in adult cardiomyocytes. Adrenergic agonists enhanced ICa, but differentially altered the CICR gain, diastolic Ca(2+), and Ca(2+)-sparks in mutant cells. The mutant cells, when Ca(2+)-overloaded, showed longer and wandering Ca(2+)-sparks that activated adjoining release sites, had larger CICR gain at -30mV yet smaller Ca(2+)-stores. We conclude that control and mutant iPS-CMs express the adult cardiomyocyte Ca(2+)-signaling phenotype. RyR2 F2483I mutant myocytes have aberrant unitary Ca(2+)-signaling, smaller Ca(2+)-stores, higher CICR gains, and sensitized adrenergic regulation, consistent with functionally altered Ca(2+)-release profile of CPVT syndrome.
    Cell calcium 05/2013; · 4.29 Impact Factor
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    ABSTRACT: Background/Aims: The association between postoperative infection and prolonged survival in high-grade glioma is still a matter of debate. Previously we demonstrated that the intracerebral (i.c.) injection of heat-inactivated staphylococcal epitopes (HISE) resulted in a well-defined infux of immunocompetent cells across the blood-brain barrier. The present study investigated the potential antitumoral effect of HISE-immunostimulation in an experimental glioma model. Methods: Wistar rats were intracerebrally implanted with 9L gliosarcoma cells (n=6), 9L cells mixed with HISE (n=12), or phosphate buffered saline (n=4). Tumor growth was measured by serial magnetic resonance imaging (MRI). After death due to the tumor burden, the brains were histopathologically assessed for inflammation and oncolysis. A toxicity assay was performed to quantify potential impairment of HISE on tumor cell growth in vitro. Results: Animals treated by HISE showed a significant increase in average survival and even complete regression of an already established mass in one case. Naïve 9L gliosarcomas failed to recruit significant numbers of systemic immune cells. In contrast, concomitant intracerebral HISE inoculation lead to a oncolysis and a distinct peri- and intratumoral infiltration of macrophages, CD8 and CD4 co-expressing T-lymphocytes in two thirds of the tumor-bearing animals. The toxicity screening showed HISE-mediated oncolysis to be ineffective ex vivo. Conclusion: This study describes a novel approach for combatting malignant glioma using inactivated staphylococci as potent immunomodulators. Our results provide an outline for investigating the strategic potential of bacteria as emerging future therapeutics.
    Cellular Physiology and Biochemistry 05/2013; 31(4-5):614-624. · 3.42 Impact Factor
  • 79. Jahrestagung der DGK, Manheim; 04/2013
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    ABSTRACT: The induction of teratoma in mice by the transplantation of stem cells into extra-uterine sites has been used as a read-out for cellular pluripotency since the initial description of this phenomenon in 1954. Since then, the teratoma assay has remained the assay of choice to demonstrate pluripotency, gaining prominence during the recent hype surrounding human stem cell research. However, the scientific significance of the teratoma assay has been debated due to the fact that transplanted cells are exposed to a non-physiological environment. Since many mice are used for a result that is heavily questioned, it is time to reconsider the teratoma assay from an ethical point of view. Candidate alternatives to the teratoma assay comprise the directed differentiation of pluripotent stem cells into organotypic cells, differentiation of cells in embryoid bodies, the analysis of pluripotency-associated biomarkers with high correlation to the teratoma forming potential of stem cells, predictive epigenetic footprints, or a combination of these technologies. Each of these assays is capable of addressing one or more aspects of pluripotency, however it is essential that these assays are validated to provide an accepted robust, reproducible alternative. In particular, the rapidly expanding number of human induced pluripotent stem cell lines, requires the development of simple, affordable standardized in vitro and in silico assays to reduce the number of animal experiments performed.
    Stem cell research 03/2013; 11(1):552-562. · 3.39 Impact Factor

Publication Stats

13k Citations
2,089.91 Total Impact Points


  • 1995–2014
    • University of Cologne
      • • Institute of Neurophysiology
      • • Department of Chemistry
      • • Center for Physiology and Pathophysiology
      • • Department of Neurology
      • • Institute of Anatomy I
      Köln, North Rhine-Westphalia, Germany
  • 2012
    • Heinrich-Heine-Universität Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2010–2012
    • Universität Konstanz
      • The Doerenkamp-Zbinden Chair of in-vitro Toxicology and Biomedicine
      Konstanz, Baden-Wuerttemberg, Germany
  • 2003–2012
    • Huazhong University of Science and Technology
      • Department of Pathology and Pathophysiology
      Wuhan, Hubei, China
    • Northeast Normal University
      Hsin-ching, Jilin Sheng, China
  • 2011
    • Nicolae Simionescu Institute of Cellular Biology and Pathology
      Bucureşti, Bucureşti, Romania
  • 2008
    • Friedrich-Schiller-University Jena
      • Clinic of Internal Medicine III
      Jena, Thuringia, Germany
  • 2006–2008
    • University of Bonn
      • Institut für Physiologie I
      Bonn, North Rhine-Westphalia, Germany
  • 2005–2008
    • Robert Koch Institut
      Berlín, Berlin, Germany
    • Justus-Liebig-Universität Gießen
      Gieben, Hesse, Germany
  • 2005–2006
    • Axiogenesis AG
      Köln, North Rhine-Westphalia, Germany
  • 2004
    • Università degli Studi di Torino
      Torino, Piedmont, Italy
  • 1995–2004
    • Institut für klinische Pharmakologie
      Stuttgart, Baden-Württemberg, Germany
  • 1999
    • University of Pennsylvania
      • Department of Animal Biology
      Philadelphia, PA, United States
  • 1997
    • Max Planck Institute of Biochemistry
      München, Bavaria, Germany
  • 1988–1996
    • Freie Universität Berlin
      • Institute of Pharmacology and Toxicology
      Berlin, Land Berlin, Germany
  • 1992–1995
    • Leibniz Institute of Plant Genetics and Crop Plant Research
      Gatersleben, Saxony-Anhalt, Germany
  • 1991–1994
    • Humboldt-Universität zu Berlin
      • Department of Biology
      Berlin, Land Berlin, Germany
  • 1982–1990
    • Universität des Saarlandes
      • Physikalische Chemie
      Saarbrücken, Saarland, Germany