Blood-forming hematopoietic stem cells (HSCs) are the source of all blood cells that are produced every day throughout the entire life. Their potential to renew the entire blood system is the key to the treatment of many hematological diseases including leukemia. To fulfill their vital function in blood regeneration, HSCs need the control by their direct microenvironment – their niche – in the bone marrow. Understanding the way, in which the niche and HSCs interact, is the fundamental basis for developing artificial stem cell niches that allow us to instruct stem cell behavior for their application in regenerative medicine.
By using tailor-made biomaterials we could show that besides biological and biochemical factors also physical parameters play an important role in determining stem cell-niche interactions. In reductionist approaches, in which we studied only one parameter at a time, we could show that matrix stiffness, nanostructure and the three-dimensional architecture of the environment influence HSC behavior. On the basis of these results we developed a simplified in vitro bone marrow analog that mimics crucial aspects of the natural stem cell niche. These systems are applied (i) for fundamental studies of the mutual interactions of HSCs and their niche in health and disease and (ii) for the development of a drug testing platform. In this way, we are taking the first steps towards a stem cell-instructive platform for regenerative medicine.