CXCR2 modulates bone marrow vascular repair and haematopoietic recovery post‐transplant. (9th March 2015)

• Record Type: Journal Article
• Authors: Hale, Sarah J. M.; Hale, Ashley B. H.; Zhang, Youyi; Sweeney, Dominic; Fisher, Nita; van der Garde, Mark; Grabowska, Rita; Pepperell, Emma; Channon, Keith; Martin‐Rendon, Enca; Watt, Suzanne M.
• Is Part Of: British journal of haematology. Volume 169:Number 4(2015:May)
• Page Start: 552
• Page End: 564
• Publication Date: 2015-03-09
• Subjects: bone marrow transplantation -- stem cell niche -- bone marrow vascular niche -- CXCL8 -- CXCR2; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.13335
• Languages: English
• ISSNs: 0007-1048

Abstract

Summary: 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.