A5103149274- 3D Printing in Biomedical Research
- Pancreatic function and diabetes
- Liver Disease Diagnosis and Treatment
- Organ Transplantation Techniques and Outcomes
- Liver physiology and pathology
- Liver Disease and Transplantation
- Drug-Induced Hepatotoxicity and Protection
- Robotic Mechanisms and Dynamics
- Metabolism, Diabetes, and Cancer
- Diabetes Management and Research
- Innovative Microfluidic and Catalytic Techniques Innovation
- Viral Infectious Diseases and Gene Expression in Insects
- Dynamics and Control of Mechanical Systems
- Diet, Metabolism, and Disease
- Pluripotent Stem Cells Research
- Advanced Chemical Physics Studies
- Drug Transport and Resistance Mechanisms
- Surface and Thin Film Phenomena
- Nanoparticles: synthesis and applications
- Cannabis and Cannabinoid Research
- Pharmacogenetics and Drug Metabolism
- Adipose Tissue and Metabolism
- Diabetes and associated disorders
- Animal testing and alternatives
- Metabolomics and Mass Spectrometry Studies
Ludwig-Maximilians-Universität München
1990-2025
Inspire
2013-2023
University Hospital of Zurich
1994-2011
University of Zurich
2004-2009
Swiss Integrative Center for Human Health
2007
Paderborn University
1985-2005
Diabetes Australia
2003
Howard Hughes Medical Institute
1999-2001
Harvard University
1999-2001
Massachusetts General Hospital
1999-2001
The endocrine cells of the rat pancreatic islets Langerhans, including insulin-producing beta-cells, turn over every 40-50 days by processes apoptosis and proliferation differentiation new islet (neogenesis) from progenitor epithelial located in ducts. However, administration to rats trophic factors such as glucose or glucagon-like peptide 1 for 48 h results a doubling cell mass, suggesting that may reside within themselves. Here we show human contain heretofore unrecognized distinct...
Glucotoxicity and lipotoxicity contribute to the impaired β-cell function observed in type 2 diabetes. Here we examine effect of saturated unsaturated fatty acids at different glucose concentrations on proliferation apoptosis. Adult rat pancreatic islets were cultured onto plates coated with extracellular matrix derived from bovine corneal endothelial cells. Exposure acid (0.5 mmol/l palmitic acid) medium containing 5.5, 11.1, or 33.3 for 4 days resulted a five- ninefold increase DNA...
Current 2-dimensional hepatic model systems often fail to predict chemically induced hepatotoxicity due the loss of a hepatocyte-specific phenotype in culture. For more predictive vitro models, hepatocytes have be maintained 3-dimensional environment that allows for polarization and cell-cell contacts. Preferably, will reflect an vivo-like multi-cell type necessary liver-like responses. Here, we report characterization microtissue model, generated from primary human liver-derived...
Many factors influence the outcome of islet transplantation. As islets in early posttransplant setting are supplied with oxygen by diffusion only and a hypoxic state portal system, we tested whether small human superior to large both vitro vivo. We assessed insulin secretion quantified cell death during conditions simulating intraportal transplant environment. In clinical setting, analyzed transplanted size on production patients type 1 diabetes. Our results provide evidence that regard show...
Previously we demonstrated the expression of long form leptin receptor in rodent pancreatic beta-cells and an inhibition insulin secretion by via activation ATP-sensitive potassium channels. Here examine islets isolated from pancreata human donors for their responses to leptin. The presence receptors on islet was double fluorescence confocal microscopy after binding a fluorescent derivative (Cy3-leptin). Leptin (6.25 nM) suppressed normal 20% at 5.6 mM glucose. Intracellular calcium 16.7...
In addition to its function as a neurotransmitter and vascular active molecule, serotonin is also mitogen for hepatocytes promotes liver regeneration. A possible role in hepatocellular cancer has not yet been investigated. Human cell lines Huh7 HepG2 were used assess the of these lines. Characteristics autophagy detected with transmission electron microscopy, immunoblots microtubule-associated protein light chain 3(LC3) p62 (sequestosome 1). Immunoblots mammalian target rapamycin (mTOR)...
Cardiomyocytes (CMs) are terminally differentiated cells in the adult heart, and ischemia cardiotoxic compounds can lead to cell death irreversible decline of cardiac function. As testing platforms, isolated organs primary from rodents have been standard research toxicology, but there is a need for better models that more faithfully recapitulate native human biology. Hence, new vitro model comprising advantages 3D culture availability induced pluripotent stem (iPSCs) origin was developed...
Abstract Although the relevance of three‐dimensional (3‐D) culture has been recognized for years and exploited at an academic level, its translation to industrial applications slow. The development reliable high‐throughput technologies is clearly a prerequisite implementation 3‐D models. In this study robustness spherical microtissue production drug testing in 96‐well hanging‐drop multiwell plate format was assessed on standard channel robotic platform. Microtissue models derived from six...
Drug-induced liver injury (DILI) cannot be accurately predicted by animal models. In addition, currently available in vitro methods do not allow for the estimation of hepatotoxic doses or determination an acceptable daily intake (ADI). To overcome this limitation, vitro/in silico method was established that predicts risk human DILI relation to oral and blood concentrations. This can used estimate if maximal concentration (Cmax) test compound is known. Moreover, ADI estimated even compounds...
To become insulin independent, patients with type 1 diabetes mellitus require transplantation of at least two donor pancreata because massive beta-cell loss in the early post-transplantation period. Many studies describing introduction new immunosuppressive protocols have shown that this is due to not only immunological events but also nonimmunological factors. test what extent hypoxia may contribute graft loss, we analyzed occurrence apoptotic and expression hypoxia-inducible factor...
A variety of explanations have been provided to elucidate the requirement large islet mass that is essential for a successful treatment patients with type I diabetes by intrahepatic transplantation. The purpose this study was investigate cell survival under effect prolonged hypoxia and/or nutrient withdrawal, which mimics posttransplantation environment transplanted islets in liver. We studied influence 24 h (1% O 2 ) intact isolated human and rat as well combined oxygen/nutrient deprivation...
<h3>Objective</h3> The purpose of this study was to assess non-invasive imaging modalities including MRI and CT compare the quantitative amount fat with data provided by pathologist a chemical lipid assay in leptin-deficient mouse livers. <h3>Methods</h3> A liver/fat phantom first used accuracy small-animal human CT, followed correlation analysis ob/ob liver quantified an accurate assay. Similarly, authors compared pathologist9s quantification automated software then investigated whether...
Macrovesicular hepatic steatosis has a lower tolerance to reperfusion injury than microvesicular with an abnormally high ratio of omega-6 (n-6): omega-3 (n-3) polyunsaturated fatty acids (PUFAs). We investigated the influence PUFAs on microcirculation in steatotic livers and potential minimize macrosteatotic liver by normalization PUFAs. Ob/ob mice were used as model macrovesicular C57/Bl6 fed choline-deficient diet for steatosis. Steatotic lean subjected 45 minutes ischemia 3 hours...
The function of the liver is well-preserved during aging process, although some evidence suggests that regeneration might be impaired with advanced age. We observed a decreased ability to restore normal volume after partial hepatectomy in elderly mice, and we identified pathway rescued was triggered by serotonin. 2,5-dimethoxy-4-iodoamphetamine (DOI), serotonin receptor agonist, reversed age-related pseudocapillarization old improved hepatosinusoidal blood flow. After hepatectomy, open...
The liver plays an important role in xenobiotic metabolism and represents a primary target for toxic substances. Many different vitro cell models have been developed the past decades. In this study, we used RNA-sequencing (RNA-Seq) to analyze following human comparison tissue: cancer-derived lines (HepG2, HepaRG 3D), induced pluripotent stem cell-derived hepatocyte-like cells (iPSC-HLCs), cancerous liver-derived assays (hPCLiS, precision cut slices), non-cancerous (PHH, hepatocytes) 3D...
Implantation of small liver grafts causes injury and defective regeneration leading to graft failure. We investigated whether Kupffer cell-dependent TNF-α signaling contributes this poor outcome. Partial 30% transplantation was performed in C57BL/6 wild-type mice (control group), three groups with down-regulation the pathway: ( i ) TNF receptor 1 knockout [TNFR-1(−/−)] mice, pretreated ii gadolinium chloride or iii pentoxifylline (PTX). Fifty-percent partial transplantation, a model...
Three-Dimensional (3D) liver microtissues, specifically prepared from primary human hepatocytes (PHH) in coculture with nonparenchymal cells (NPCs), have been shown to be a valuable tool for
Previously we demonstrated the superiority of small islets vs large in terms function and survival after transplantation, generated reaggregated rat (pseudo-islets) standardized dimensions by hanging-drop culture method (HDCM). The aim this study was to generate human pseudo-islets HDCM evaluate compare physiological properties pseudo-islets. Isolated were dissociated into single cells incubated for 6-14 days HDCM. Newly formed analysed dimensions, morphology, glucose-stimulated insulin...
Extensive DNA sequencing has led to an unprecedented view of the diversity individual genomes and their evolution among patients with clear cell renal carcinoma (ccRCC). To understand subclonal architecture dynamics patient-derived two-dimensional (2D) three-dimensional (3D) ccRCC models in vitro, order determine whether they mirror inter- intratumor heterogeneity. We have established a comprehensive platform living cancer from surgical specimens. confirmed concordance 2D 3D (PDC) original...
Hazard assessment, based on new approach methods (NAM), requires the use of batteries assays, where individual tests may be contributed by different laboratories. A unified strategy for such collaborative testing is presented. It details all procedures required to allow test information usable integrated hazard strategic project decisions and/or regulatory purposes. The EU-ToxRisk developed a provide regulatorily valid data, and exemplified this using panel > 20 assays (with 50 endpoints),...
Nano and microplastics are defined as particles smaller than 100 nm 5 mm respectively. The widespread production use of plastics in everyday life has resulted significant accumulation plastic debris the environment. Over last two decades there increased concerns regarding potential entry human body with ingestion being one most important routes exposure. However, magnitude nature toxic effects exposure to health is not yet fully understood. liver body's principal detoxification organ...
The implantation of grafts below 30% the normal liver volume is associated with a high risk failure known as small-for-size (SFS) syndrome. Strategies to rescue small may have dramatic impact on organ shortage. Serotonin potent growth factor for liver. goal this study was determine whether enhanced serotonin signaling could prevent deleterious effects SFS We performed transplantations in wild-type C57/BL6 and interleukin-6 (IL-6)−/− mice. Some animals received α-methyl-5-HT (DOI), an agonist...