Heparinized crosslinked collagen structures for the expansion and differentiation of hematopoietic stem cells

It is generally accepted that bone marrow contains niches that regulate the activity of hematopoietic stem cells (HSCs). These cells are the source of all different blood cells. In their niche the HSCs are localized in a specific microenvironment, where they interact with stromal cells, extracellular matrix (ECM) components and molecules like cytokines, chemokines and growth factors. The objective of the studies presented in this thesis was to develop a bioreactor system, in which the bone marrow is mimicked, for the controlled expansion and differentiation of HSCs and hematopoietic progenitor cells (HPCs). Such a system is expected to facilitate an effective expansion of HSCs and to provide a model for investigating the mechanisms of hematopoiesis and processes such as stem cell mobilization and homing. The in vitro expansion and controlled differentiation of HSCs and HPCs is of great interest for application in bone marrow transplantation. Additionally, controlled differentiation of these cells can be used to produce blood cells for transfusion. The focus will be on the expansion of HPCs and their differentiation into erythroid cells.