Human Stem Cell Derived Liver Cells for Disease Modeling and Whole Organ Engineering

The vital blood system in mammals is continuously regenerated throughout life by a process called hematopoiesis. In hematopoiesis, a stem cell population called hematopoietic stem cells (HSC’s) undergo differentiation and produce specialized mature blood cells including red blood cells, megakaryocytes and myeloid cells. Even a small failure in this process can result in hematological disorders such as anemia and leukemia. Transplantation of HSCs into patients to reconstitute cellular compartments of the blood strictly relies on the expansion of HSCs in vitro conditions. The expansion of HSC population remains as a main challenge in the field, as the self-renewal capability of HSCs is very limited in vitro conditions. The goal of this thesis project is to develop hydrogel-based 3D culture system, that would provide appropriate biochemical and biomechanical signals to encapsulated HSC’s for their efficient expansion, without losing their pluripotency. Molecular and mechanical constituents of the murine fetal liver HSC niche between day 12 and 16 of the development have already defined in previous studies. The next step is to create a novel in vitro 3D culture system by translating previously acquired molecular and mechanical signals in hydrogel-based platform. To achieve this, nanoindentation protocols will be developed for in depth micro-mechanical characterization of fetal liver and hydrogel structures, as well as chemical strategies for conjugating biocryptic molecules to the hydrogel networks to enhance biomimetic potential.