Description of the research focus
Recent progress in stem cell technologies has opened new doorways to investigate human biology in health and disease as well as the development of therapeutic applications. Current investigations on 3D stem cell derived organoids and tissues conquer a variety of major hurdles of in vitro research. The fundament for 3D in vitro models of non-mammalian and mammalian cells was established over a century ago with dissociated and re-aggregating marine sponge cells. The mechanism behind the ability of cells to form free-floating spheroids, which requires the skills to self-adhere and self-organize is strongly linked to in vivo occurring embryonic processes.
Since the early days of pluripotent stem cell research, one of the most commonly known 3D differentiation system is represented by the embryoid body formation from pluripotent stem cells (PSCs), the in vitro counterpart of the early gastrula. 3D culture and differentiation approaches of multipotent stem cells of different origin are meanwhile widely used either with one type of stem cells, like neural stem cells (NSCs), mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs) or in a combination of different stem cells (e.g. HSCs and MSCs) to study stem cell niches.
An exciting breakthrough in stem cell associated 3D formation was the generation of cortical structures from mouse embryonic stem cells (ESCs) in suspension culture. In the recent decade, numerous groups have reported the generation of a broad variety of 3D self-organizing organ-like structures from mouse and human stem cells. Thus, the term “organoid” has become generally accepted in the scientific community. Organoids are defined as 3D cellular structures exhibiting function and morphology approximated to the respective in vivo counterpart.
Today it is widely accepted that 2D cultures have their limitations. Results obtained with 2D and 3D assays can differ substantially, with the latter providing data that are in many circumstances physiologically more relevant. The value and usability of complex organoids derived from human-PSCs has been proved for numerous tissues from all germ layers, including pancreas, liver, gut, lung, kidney brain], or retina. 3D systems position in vitro studies even closer to the in vivo situation and may in the future reduce the use of animals in research and therapeutic testing.
The technology of microfluidic devices (CHIPS) shows many advantages in different aspects compared to conventional in vitro systems. Our members use most of the main stem cell sources [induced pluripotent (iPSCs), ESCs, MSCs, NSCs and HSCs], and our interdisciplinary research training program will address questions pertaining to cell specification, morphogenesis and differentiation as well as to mechanisms involved in human diseases and cell-based therapies. Research with easily accessible in vivo 3D systems, such as the chick embryo (in ovo) completes our comprehensive network. In addition, we have implemented and established a variety of technical and biological approaches within the CrispR/CAS technology, which is managed by our lately founded “CrispR/CAS task force”.
Nevertheless, the development of novel therapeutic strategies in the fields of cell- and gene therapy strongly depends on the understanding of signaling processes that regulate development, cell function and dysfunction on a molecular level in the diverse tissues and organs. Our program combines 3D systems of different stem cell types and culture conditions as well as a spectrum of genetic, biochemical, molecular and cell biology approaches to investigate cues of signaling in development and pathological modifications in disease conditions and is well equipped to address these questions.
In addition, several projects within the research program will pave the way toward translational applications. The University of Tübingen therefore plans a research training group with the title: ‘Stem Cells in 3 Dimensions: Modeling Molecular Mechanisms of Development & Disease’.
