A core competence of the Department »Cell Biology and Tissue Engineering« is the establishment and optimisation of special cell culture techniques in 2D (2-dimensional) and 3D (3-dimensional). These cell and tissue systems were designed and developed for application in therapy, diagnostics and pharmacology. The aim was to enable the cells to generate tissue structures purely intrinsically, e.g. generating 3D cartilage-like microtissues using a special culture system mimicking the first step of chondrogenesis in vertebrates, the condensation of mesenchymal cells.
Tissue engineering of in vitro cartilage tissue for cell-based therapy
Cell-based therapies to regenerate functional tissues are the primary goal of regenerative medicine. This can be achieved by applying single cells in suspension or by transplanting tissues which have already been produced in vitro. Research and development goal is the optimization of the production process of "microtissues" for the regeneration of cartilage defects (e. g. trauma, arthrosis) by the body's own cells. The challenges here are the cultivation of freshly isolated articular cartilage cells (primary cells), their proliferation in culture and the chondrogenic differentiation in "microtissues". The in vitro tissues are produced without scaffolds in order to obtain a purely autologous product.
An autologous transplantation has the fewest side effects, but this approach does not always produce functional cartilage. A challenge in cell-based cartilage regeneration therapies is the identification of a ‘‘personalized diagnostic tool’’ to predict the chondrogenic potency of cells from patients who are going to be treated with autologous cells. Using our three-dimensional (3D) cell culture technique we could show clear differences in chondrogenic potential among individual donors whereas cells in 2D culture exhibited an identical chondrocyte profile. Therefore, our microtissue model might be the basis for an in vitro platform to predict the therapeutic outcome of autologous cell-based cartilage repair and/or a suitable tool to identify early biomarkers to classify the patients (Martin et al., 2017, Featured Article).
Investigation and diagnosis of osteoclast-specific diseases
Better knowledge of skeletal cell biology is the basis for understanding bone-specific diseases, such as osteoporosis, arthritis, and genetic conditions that affect bone growth and bone aging. Dr. Lutter studies how the skeletal cells function, how they communicate and regulate one another, with focus on the bone-resorbing osteoclast. Osteoclasts are large, mobile cells that begin their life as mononuclear hematopoietic cells. Under the influence of specific growth factors (MCSF and RANKL), the precursors can migrate to the site of bone resorption, attach tightly to the bone and secrete bone dissolving factors. To study how osteoclasts behave in natural habitat we developed an approach to assemble a bone-like extracellular matrix derived by human osteoblasts (ODEM, Lutter et al., 2010 Journal of Cellular Biochemistry). This special experimental setup enables our group to connect bone and cartilage research in a novel way.
In vitro tissue model for pharmacology
In order to test the effect of drugs on joint cartilage, work is currently underway on the development of an in vitro tissue model, since the cartilage-typical physiology results primarily from the tissue formation with its typical extracellular matrix. A particular challenge in this project is the availability of cartilage cell lines that can be cultivated and propagated over a longer period of time with constant quality. To this end, methods for extending the lifespan and cell division as well as the generation of induced pluripotent stem cells (iPS) are used to develop cartilage cell lines. If required, these are then available at any time for the engineering of microtissues.
Cell-based test systems for the diagnosis of autoimmune diseases
In autoimmune diseases antibodies of a person’s own immune system are directed against the body's own structures. These diseases include e.g. type 1 diabetes and multiple sclerosis.A characteristic feature of autoimmune diseases is the formation of disease-specific autoantibodies (AAK) that are used as diagnostic markers. These autoantibodies are detected, for example, by fluorescence-based labelling of the appropriate antigen structures in cells. Special challenges in this process are suitable, well-characterized cell lines or freshly isolated cells, a preparation technique of the cells that guarantees the most comprehensive detection of the possible target structures of the AAKs, as well as an automated evaluation of the test system. These projects are carried out in close cooperation with Generic Assays GmbH in Dahlewitz.