Thesis defense Yvonne Dorland: Crosstalk in the bone marrow

On  21 January 2020 (12:00) Yvonne Dorland will defend her thesis 'Crosstalk in the bone marrow. Her research reveals new molecular processes involved in the interaction between endothelial, hematopoietic and mesenchymal stromal cells, which contributes to our understanding of bone marrow function.

The bone marrow consists of many components, including hematopoietic stem and progenitor cells (HSPCs) that produce blood cells, stromal cells which have a supportive function, and endothelial cells forming the interior vascular wall.

Mesenchymal stromal cells (MSCs) provide structural support to all bone marrow cells and instructive signals to guide hematopoiesis and are applied in a variety of cellular-based therapies. Matured blood cells cross the vascular wall, out of the bone marrow into the circulation. In this thesis, the interactions between HSPCs, MSCs, the endothelium and the bone marrow microenvironment are investigated.

Hematopoiesis support

First, we explored the effect of the extracellular matrix protein TGFBI expression by MSCs and hematopoietic cells and found that a balanced expression of TGFBI in the bone marrow niche supports hematopoiesis. Furthermore, we uncovered that Lamin A/C expression defines the nuclear shape and the migration capacity of MSCs in vitro and viable retention of administered MSCs in vivo.

Endothelial integrity

During migration of MSCs, hematopoietic or immune cells across the endothelial barrier, an accurate response at the endothelial cell-to-cell contacts is required to protect the vasculature. We found that the F-BAR protein pacsin2 protects endothelial integrity during dynamic remodeling by inhibiting the internalization of cell-cell contact proteins. Finally, we examined how cell density and matrix rigidity affect the formation of the cell-cell contacts between cultured MSCs.

Promotor: Prof CE van der Schoot MD PhD

Copromotores: S Huveneers PhD and C Voermans PhD

Venue: University of Amsterdam, Agnietenkapel