Investigating how VCAM-1+ sinusoidal endothelial cells regulate hematopoietic stem cell trafficking

Although hematopoietic stem cells (HSCs) have been successfully used in transplantation therapies for more than 50 years, we still do not have a complete mechanistic understanding of the factors that regulate HSC trafficking and engraftment. Recent findings in the Forsberg lab indicate that the vascular endothelium plays important roles in regulating HSC trafficking into and out of bone marrow niches. We hypothesized that sinusoidal endothelial cells marked by the adhesion molecule VCAM-1 mediate the trafficking of HSCs from blood to bone marrow and from bone marrow to blood. Using in vitro transendothelial migration assays, I show that blocking VCAM-1 on HSCs, using blocking antibodies, significantly impairs the ability of HSCs to migrate through endothelial cell layers. These results suggest that VCAM-1 on HSCs is important for HSC extravasation and provide insight into what may be happening in vivo when HSCs must interact with endothelial cells to migrate into and out of the bone marrow