Blood is replenished with billions of fresh cells every day throughout the entire life span. The source of these cells are the hematopoietic stem cells (HSCs). Their ability to reconstitute the entire blood system makes them the key to the cure of many hematological diseases. However, this treatment is restricted by the limited availability of HSCs. To overcome that limitation, controlling HSC behavior in terms of proliferation or differentiation in vitro, is an important goal of nowadays HSC research.
In vivo HSCs are controlled by a highly specialized microenvironment – the niche – within the bone marrow. In this niche HSCs are supported by mutual cell-cell as well as cell-matrix interactions. While it is clear that biological and/or chemical parameters play an important role in this interplay, surprisingly little attention was paid to physical signals that are transmitted by the niche microenvironment. In the last years, we found that these physical signals include matrix stiffness, nanostructure as well as the three-dimensional architecture. In reductionist approaches, in which we studied only one parameter at a time, we could show that all of these parameters impact HSC behavior. These studies helped us to develop simplified in vitro bone marrow analogs.
Currently, we apply these systems to study the interplay of human HSCs and their microenvironment in health and disease, by mimicking the niche not only under steady-state conditions but also during bone marrow infections or malignant diseases. With these studies we want to gain a fundamental understanding of the role of stem cell niches in disease onset and progression.