Directed differentiation of pancreatic stem cells by soluble and immobilised signalling factors

Recent findings demonstrate that adult stem cells exhibit a much higher differentiation potential than previously expected and that the sources within the adult organism seem to be surprisingly manifold. In this study, we investigated adult stem cells isolated from mouse and rat pancreas and showed for the first time their potential to differentiate towards osteoblasts, chondrocytes and adipocytes. These pancreatic stem cells (PSCs) have previously been described to differentiate spontaneously into cell types of all three germ layers. We could now demonstrate that a directed differentiation is also possible and compared a variety of cytokines as inducers. In addition to today's practice of applying only soluble differentiation factors we investigated the use of immobilised cytokines. For protein immobilization different strategies were evaluated such as covalent linkage of insulin-like growth factor-1 (IGF-1) to amino- or epoxy-silanised glass or affinity binding of the biotinylated cytokine to neutravidin-coated surfaces. Our results show that cytokines could be immobilised functionally, retaining their biological activity to effectively induce stem cell differentiation in long-term cell culture experiments. Our results emphasised the high differentiation potential of mouse and rat PSCs, showing that a directed cytokine-induced differentiation of both rodent PSC types is possible and demonstrating that differentiation factors, immobilised to different surfaces, can successfully trigger a stem cell's fate.