A central issue in biomedical research is the need to carry out studies and genetic manipulations of specific types of human and animal cells. Many of these like primary neurons or cardiomyocytes are difficult to obtain directly from living tissues. Recent advances using pluripotent cells have made it possible to generate diverse specialized cell types from stem cells, or induced pluripotent stem cells (iPSs).
Alongside assisting groups with experiments, the facility is putting a strong emphasis on training, says Sebastian Diecke, who heads the facility. “ Hosted by the BIH we have already conducted two courses for diverse groups of students, postdocs, and group leaders and will enlarge these activities as we go along,” he says. “At the moment we’d like to encourage anyone who is interested to come by and see what’s possible.”
Sebastian did his PhD at the MDC in the group of Daniel Besser, who now heads the office of the German Stem Cell Network, located at the MDC. In Daniel’s group, Sebastian carried out basic research on human and mouse embryonic stem cells before moving on to Stanford in the US on a postdoctoral fellowship. There he worked at the Cardiovascular Institute (CVI), focusing on disease modeling using induced pluripotent stem cells and helping to establish a pluripotent stem cell core facility much like the one being set up here.
“At Stanford I was mainly interested in different types of heart disease called cardiomyopathies. We learned to optimize the procedures by which cardiomyocytes were derived from induced pluripotent stem cells. The aim is to elucidate the underlying mechanisms of diseases using isogenic cell lines generated with state-of-the-art differentiation protocols and genome engineering techniques, combined with multiple downstream analysis of gene functions.”
During his Stanford period, Sebastian maintained contact with the MDC and was excited to hear that Berlin will establish a new institute focusing on translational research. He reached out to the MDC to ask if they would consider establishing a pluripotent stem cell core facility together with the BIH. At the time, preliminary discussions about the establishment and structure of the BIH were taking place, and it became clear that such a facility would be a valuable platform for interactions and services for scientists of the MDC and Charité. Sebastian was ideally qualified to head the new facility.
Work with iPS cells is different from the use of embryonic stem cells in that they are considered free of ethical issues and can be derived from nearly every tissue from the human body. Combined with the latest differentiation and gene manipulation techniques, Sebastian says, they are powerful tools for disease modeling, tissue engineering and drug screening approaches.
“Currently we are focusing on establishing various neuronal and cardiac differentiation protocols and setting up a pipeline for targeted gene manipulations like knockout, overexpression studies or introduction of specific point mutations related to diseases,” he says. “Using isogenic cell lines with defined genetic backgrounds might help us to elucidate the precise underlying mechanisms by which the symptoms of these diseases arise.”
The group is currently housed in room 32 on the ground floor of the Walter Friedrich House on the Buch campus. Various services are already available, and the group is eager to establish new collaborations with labs from the BIH, MDC and Charité. Such projects can take different forms: a group may send someone to work in the facility to optimize a particular cell differentiation or modification protocol, or simply come by for advice.
One long-term aim, Sebastian says, is to connect the facility with similar platforms across Germany. The German Stem Cell Network will facilitate such partnerships, permitting groups to exchange expertise in working with different types of cells and establishing standards for the various cell lines. Standardized protocols are crucial for reasons of experimental reproducibility – you need to be able to compare the results obtained by different labs in order to extract the right information or to plan additional experiments, and that is heavily influenced by the way the cells are prepared.”
“Work in human and animal cell cultures is an essential step in the discovery of gene functions and their relation to disease,” Sebastian says. “Most groups will, at some point, need to work with such cells. Creating a facility is a way to make it easier for them to do so and carry out their projects at a high level of quality.”
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