CXCR2 modulates bone marrow vascular repair and haematopoietic recovery post-transplant

British Journal of Haematology
Sarah J M HaleSuzanne M Watt

Abstract

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 therapeu...Continue Reading

References

Mar 1, 1978·Experimental Cell Research·B L Carter, M N Jagadish
Jul 25, 2000·European Journal of Clinical Investigation·P M RoodC E van der Schoot
Aug 22, 2000·The Journal of Investigative Dermatology·R M DevalarajaA Richmond
May 20, 2003·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Snjezana MilatovicAnn Richmond
Jun 12, 2003·Annals of the New York Academy of Sciences·Shahin RafiiKoichi Hattori
Feb 24, 2006·Nature Reviews. Immunology·Anne Wilson, Andreas Trumpp
Jul 9, 2009·International Journal of Cancer. Journal International Du Cancer·Seema SinghRakesh K Singh
Jul 31, 2010·Biotechnology and Bioengineering·Bita CarrionAndrew J Putnam
Apr 27, 2011·Tissue Engineering. Part C, Methods·Cheen Peen KhooSuzanne M Watt
Mar 1, 2012·Journal of Carcinogenesis·Kalyan C NannuruRakesh K Singh
Mar 29, 2012·Inflammation & Allergy Drug Targets·Tatsuki Sugiyama, Takashi Nagasawa

❮ Previous
Next ❯

Citations

Apr 28, 2016·Seminars in Cell & Developmental Biology·Jonathan LeorTal Konfino
Mar 30, 2017·The Journal of Experimental Medicine·Bradley W BlaserLeonard I Zon
May 16, 2019·The Journal of Clinical Investigation·Darja KarpovaJohn F DiPersio

❮ Previous
Next ❯

Methods Mentioned

BETA
FCS
Antibody Arrays
biopsies
fluorescence microscopy
flow cytometry
ELISA

Software Mentioned

Angiosys
FACS Diva
Axiovision
Simple PCI
Adobe Photoshop
ImageJ

Related Concepts

Related Feeds

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.