Sophia Meermeyer (Hannover, DE), Arundhati Joshi (Bremen, DE), Prof. Dr. Dorothea Brüggemann (Bremen, DE), Prof. Dr. Cornelia Lee-Thedieck (Hannover, DE)
Abstract text (incl. figure legends and references)
Introduction
Hematopoietic stem and progenitor cells (HSPCs) are indispensable for treating many hematological malignancies. Recreating their natural microenvironment – their niches – in vitro is one potential way to gain control and program their behavior ex vivo. Besides the endosteal niche close to the endosteum, perivascular niches were described in the vicinity of small blood vessels including bone marrow sinusoids, which are are specialized, single-cell-walled, fenestrated blood vessels with a discontinuous basal lamina.
Objectives
In the current project, we aimed to mimic vascular HSPC niches at bone marrow sinusoids, with particular emphasis on their microvascular nature and the specialized basal lamina.
Methods
Nanofibrous fibrinogen scaffolds were used to mimic the basal lamina of bone marrow sinusoids. The biomaterial was seeded with microvascular endothelial cells from one and mesenchymal stem/stromal cells from the other side to mimic the inner endothelial layer of microvasculature and the outer layer of vessel-associated stromal cells, respectively. HSPCs were introduced to either the stromal or the endothelial side to imitate residing in or homing to the niche.
Results
We observed that HSPCs proliferate more in triple cocultures than in double or single cultures on the scaffolds. Furthermore, maintenance of the HSC marker CD34 and abundance of hematopoietic cytokines were affected by presence of scaffolds and the different cell types in double and triple cocultures. The layered model of the vascular niche allowed migration of HSPCs through the scaffold, showing that the nanofibrous fibrinogen scaffolds are a suitable model for the fenestrated basal lamina.
Conclusions
The presented model mimics crucial aspects of bone marrow sinusoids of vascular HSPC niches and allows investigations of related cell-cell and cell-matrix interactions. Thus, this model is one step towards the goal of functional, biomimetic models of the vascular HSPC niche.