Bone marrow mesenchymal spheres as potential support for the expansion of hematopoietic stem cells for allogeneic stem cell transplantation

The human adult bone marrow consists of various cell types, as hematopoietic stem and progenitor cells (HSPCs) being the primary cellular component regulated by osteoblasts, osteoclasts, endothelial cells, non-myelinating Schwann cells, sympathetic nerves, macrophages, and mesenchymal stromal cells (MSCs) (Morrison & Scadden, 2014). Strategies to increase HSPC numbers for allogeneic stem cell transplantation include ex vivo expansion using MSC based co-culture systems. However, the data available suggest that conventional plastic‑adherent MSCs fail to preserve primitive HSPCs. Recently, we established a novel method to isolate and culture human MSCs as non-adherent bone marrow mesenchymal spheres.

The project aims on functional characterization of bone marrow derived mesenchymal spheres and their matrix with respect to control HSPC proliferation and differentiation.

Our specific objectives are (i) to investigate mechanisms potentially responsible for HSPC support. Accordingly, we plan to elaborate candidate factors that determine expansion of HSPCs. Furthermore, we will study the interaction between HSPCs and extracellular matrix components produced by human bone marrow mesenchymal spheres. In parallel we plan (ii) to investigate effects of co-cultured mesenchymal spheres on homing and HSPC engraftment using a previously established xenograft model.

Participating group members:

Martin Bornhaeuser, Manja Wobus, Steffanie Tietze, Martin Kraeter, Katrin Mueller, Kristin Heidel