CD133+ Endothelial Cells Isolated From Venous Malformation Recapitulates Clinical Phenotype in a Mouse Model
Peter Grzesik, DO, Andrew K. Edwards, PhD, Alison K. Kitajewski, BA, Carrie J. Shawber, PhD, June K. Wu, MD.
Columbia University, New York, NY, USA.
Venous malformations (VMs) are a congenital disorder of the venous vasculature that can cause disfigurement and life-threatening coagulopathy. Treatment options range from sclerotherapy to surgical debulking and are often empirical. Development of biologically-targeted therapy is limited as the origin of VMs has yet to be identified. We hypothesized that VMs may have a progenitor cell origin similar to infantile hemangioma or lymphatic malformations.
A resected VM specimen was digested and cells sorted with CD133+ magnetic beads. Isolated cells were analyzed by FACS with antibodies against endothelial progenitor markers, inflammatory cell markers, and differentiated EC markers. Cells were re-suspended in Matrigel and injected into an immunocompromised mouse. After 3 weeks, implants were harvested and stained with an antibody against ECs marker, CD31.
CD133+ VM cells expressed endothelial progenitor cell markers CD34, CD90, CD146, endothelial cell markers CD31, VE Cadherin, VEGFR2, VEGFR3 (Figure1). Expression of CD45 (lymphocyte marker) and CD11b (macrophage marker) was not observed. In the mouse model, CD133+ VM cells formed dilated vascular channels (Figure 2, Panel B) lined by CD31+ cells (Figure 2, Panel D), recapitulating the clinical phenotype (Figure 2, Panel A&C)).
VMs contain a CD133+ population of cells that express both endothelial progenitor and mature markers, suggesting that VM endothelial cells (EC) are immature and poorly differentiated. VM ECs when implanted in mice recapitulate the VM phenotype observed in patient specimens. This mouse model can be used as a pre-clinical model to study potential therapeutics and investigate if VMs are arising from a progenitor cell.
Back to 2017 Program