Wissenschaftlicher Kongress am Samstag, 27. Oktober 2018 in Köln

Prof. Thomas Hartung

Prof. Dr. Thomas Hartung MD, PhD, Professor für Pharmakologie und Toxikologie an der Universität Konstanz, Director CAAT US and Europe, Professor of Evidence Based Toxicology at the Johns Hopkins University Bloomberg School of Public Health, Baltimore, USA

Prof. Thomas Hartung

Prof. Dr. Dr. med. Thomas Hartung, MD PhD ist Lehrstuhlinhaber für Evidenz-basierte Toxikologie und Professor für Umweltgesundheit und -technik, sowie für Molekular Mikrobiologie und Immunologie an der Johns Hopkins Bloomberg School of Public Health, Baltimore. Außerdem hat er eine Professur für Pharmakologie und Toxikologie an der Universität Konstanz inne und ist Direktor von CAAT (Center for Alternatives to Animal Testing). Er ist der ehemalige Leiter des Europäischen Zentrums für die Validierung alternativer Methoden (ECVAM) und hat mehr als 500 wissenschaftliche Publikationen verfasst. 

Prof. Dr. Dr. med. Thomas Hartung, holds a chair for evidence-based toxicology, in the department of environmental health and engineering, with a joint appointment for molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, Baltimore. He is also professor of pharmacology and toxicology at the University of Konstanz as well as director of CAAT (Center for Alternatives to Animal Testing). He is the former head of the European Center for the Validation of Alternative Methods (ECVAM) and has authored more than 500 scientific publications.
 

Abstract

Die Erforschung neurologischer Erkrankungen mit dem Mini-Gehirn aus dem Labor

The study of neurological diseases with laboratory-grown mini-brains

 
Thomas Hartung, Johns Hopkins University CAAT

Technological advances over the last decades now give us access to high-quality human cells from stem cells and increasingly to culture these in organotypic conditions to form microphysiological systems. This allows to progress towards modeling and testing also of chronic and complex systemic diseases. The example of the creation of human ‘mini brains’ from stem cells shows how these models could prove instrumental in efforts to study neurological diseases and reduce animal testing. We recently described the first model, which is standardized in size and composition and thus allows substance testing. The neurons of these 3-dimensional organoids communicate spontaneously by neurotransmitters and electrical depolarisation. This allows combining them with a micro-electrode array (MEA) to monitor key brain functionality non-invasively. By forming these mini brains from different patient’s cells allows, for the first time, to study individual susceptibilities to toxicants. Patients, who developed a disease, obviously have the genetic make-up rendering them sensitive. 
This new approach can further be amplified by embracing mini-organs on chips. The human body has more than 200 cell types, many of which can now be cultured. But as a pile of bricks is not a house, a bunch of cells is not an organ and certainly not an organism. The game-changer is that bioengineers and biologists are beginning to build functional mini-organs (microphysiological systems with organ functionalities) and putting them together with microfluidics.It is important that this new method not only enables toxicity testing but various disease models. Mini-brains are the most promising tools to study infection of the (developing) human brain with infectious agents like Zika virus, HIV, JC virus or malaria. A breakthrough development is that these mini-organs can also be frozen and still show functions such as neurite outgrowth after thawing. Freezing mini-brains allows to stock-pile them, test their quality and then send them to where they are needed the most. We can produce thousands of identical mini-brains for testing drugs and secondly, we also have functional glia cells present, which play an important role e.g. in HIV infection. Ongoing studies allow assessing, for example the damage to brain development that genes and chemicals associated with autism exert. Collaborative work into Parkinson’s and Alzheimer’s disease, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, trauma, stroke and brain cancer are on the way.