The endothelial cell microenvironment in spleen
Hematopoietic stem cells hold great promise for regenerative medicine. Information on their development, maintenance and self-renewal provides a conceptual framework for all types of adult stem cells.
Bone marrow is a rich source of hematopoietic stem cells, and for decades bone marrow transplants have provided stem cells for regeneration of the hematopoietic system. Niches for hematopoietic stem cells in bone marrow have been described as either ‘osteoblastic’ or ‘vascular’ in nature. Studies on hematopoiesis in extramedullary, non-bone marrow sites, like spleen should clarify the role of endothelial cells in niche formation, and the molecular mechanisms involved in stem cell maintenance, self-renewal and differentiation. Several recent reports have shown how infusion of isolated endothelial cells can support recovery of patients following myeloablation or radiotherapy.
This project investigates niches for extramedullary hematopoiesis in spleen which are vascular in nature. The STX3 stromal cell line derived in this lab is used as a model system. It reflects an immature endothelial cell type from spleen that supports hematopoietic stem cell maintenance, self-renewal and differentiation in vitro. Using 5G3 as a model, we are identifying endothelial progenitors that can reconstitute ectopic niches in mice and so establish hematopoiesis.
The importance of this study lies in the development of methodology to improve the clinical outcomes of stem cell therapy. A future goal will be to hasten hematopoietic recovery after myeloablative treatments by expanding stem cell niches in patients, or by establishing artificial niches for expansion of hematopoietic stem cells in vitro ahead of transplantation. It is therefore important to fully define the niches supporting hematopoietic stem cell proliferation and differentiation in terms of their cellular and molecular composition.