Hematopoietic stem and progenitor cells (HSPCs) are widely used for the treatment of hematologic diseases, as they are able to reconstitute all cells of the human blood system. Recreating their natural microenvironment using in vitro models, allows gaining control and programming HSPC behavior ex vivo. Commonly, two bone marrow (BM) HSPC niches are described: the endosteal niche near the endosteum of the bone and the vascular niche close to sinusoidal blood vessels. Characteristic for these thin and fenestrated vessels is the single layer of endothelial cells (ECs) as well as the discontinuous basal lamina.

In the current project, nanofibrous fibrinogen scaffolds were used to mimic this basal lamina of BM sinusoids. One side of the biomaterial was seeded with microvascular ECs to recapture the inner layer of the blood vessel. On the other side, mesenchymal cells mimicked the outer layer of the vessel. ECs as well as mesenchymal cells are essential supporter cell types for HSPCs in the vascular niche. To complete the in vitro model, HSPCs, isolated from the umbilical cord, were introduced to either the EC side or the mesenchymal cell side to imitate residing in or homing to the niche. In the triple co-cultures on the scaffolds, enhanced HSPC proliferation was found compared to the double or single cultures. Besides, the presence of the scaffold as well as the different cell types in double and triple cultures affected the maintenance of the HSC marker CD34 and the abundance of hematopoietic cytokines. Additionally, migration of HSPCs through the scaffold was observed, demonstrating the suitability of nanofibrous fibrinogen scaffolds as a fenestrated basal lamina mimic.

Utilizing this model, the behavior and interaction of the different cell types in the vascular niche could be investigated in the future. An artificial HSPC niche could also serve as valuable reproducible platform for drug testing, being easily accessible for analysis.