Murine models of bone marrow transplantation show that pre-conditioning regimens affect the integrity of the bone marrow endothelium and that the repair of this vascular niche is an essential pre-requisite for successful haematopoietic stem and progenitor cell engraftment. Little is known about the angiogenic pathways that play a role in the repair of the human bone marrow vascular niche. We therefore established an in vitro humanized model, composed of bone marrow stromal and endothelial cells and have identified several pro-angiogenic factors, VEGFA, ANGPT1, CXCL8 and CXCL16, produced by the stromal component of this niche. We demonstrate for the first time that addition of CXCL8 or inhibition of its receptor, CXCR2, modulates blood vessel formation in our bone marrow endothelial niche model. Compared to wild type, Cxcr2(-/-) mice displayed a reduction in bone marrow cellularity and delayed platelet and leucocyte recovery following myeloablation and bone marrow transplantation. The delay in bone marrow recovery correlated with impaired bone marrow vascular repair. Taken together, our data demonstrate that CXCR2 regulates bone marrow blood vessel repair/regeneration and haematopoietic recovery, and clinically may be a therapeutic target for improving bone marrow transplantation.

Original publication

DOI

10.1111/bjh.13335

Type

Journal article

Journal

Br J Haematol

Publication Date

05/2015

Volume

169

Pages

552 - 564

Keywords

CXCL8, CXCR2, bone marrow transplantation, bone marrow vascular niche, stem cell niche, Angiogenic Proteins, Animals, Bone Marrow, Bone Marrow Transplantation, Cell Line, Hematopoiesis, Hematopoietic Stem Cell Transplantation, Human Umbilical Vein Endothelial Cells, Humans, Mice, Mice, Knockout, Neovascularization, Physiologic, Receptors, Interleukin-8B, Transplantation Conditioning