Hematopoietic stem cell repopulating ability can be maintained in vitro by some primary endothelial cells

Abstract

Objective: Murine hematopoietic stem cells (HSC) reside primarily in bone marrow but freely circulate throughout the systemic circulation with retention of transplantable hematopoietic repopulating ability. The mechanisms maintaining HSC potential during systemic circulation remain elusive. We hypothesized that vascular endothelial cells (EC) play an important role in maintaining circulating HSC repopulating ability.

Methods: Using Tie2-green fluorescence protein transgenic mice, we have isolated primary EC populations derived from several nonhematopoietic organs and cocultured bone marrow Sca1+c-Kit+lin- cells for 7 days in the presence or absence of growth factors.

Results: All cocultures promoted the growth of hematopoietic progenitor cells at day 7 of coculture in the presence of added growth factors. Compared to fresh sorted cells, brain and heart EC monolayers significantly increased, lung and liver EC monolayers maintained, and kidney EC monolayer markedly decreased the number of colony-forming unit-spleen day-8 colonies in the 7-day cocultures. HSC competitive repopulating unit activity was maintained during the heart and liver EC 7-day cocultures but was lost in the kidney EC coculture in vitro.

Conclusion: These results demonstrate that some but not all primary EC isolated from nonhematopoietic organs support HSC function ex vivo.