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

Area of Science:

• Hematology
• Stem Cell Biology
• Vascular Biology

Background:

• Hematopoietic stem cells (HSC) circulate systemically but mechanisms maintaining their potential are unclear.
• Vascular endothelial cells (EC) are hypothesized to play a role in preserving HSC function during circulation.

Purpose of the Study:

• To investigate the role of nonhematopoietic organ-derived EC in maintaining HSC repopulating ability.
• To determine if different EC populations differentially affect HSC function ex vivo.

Main Methods:

• Primary EC were isolated from various nonhematopoietic organs of Tie2-green fluorescence protein transgenic mice.
• Bone marrow Sca1+c-Kit+lin- cells were cocultured with EC monolayers for 7 days.
• Hematopoietic progenitor cell growth and HSC competitive repopulating unit activity were assessed.

Main Results:

• Cocultures with growth factors promoted hematopoietic progenitor cell growth.
• Brain and heart EC increased, lung and liver EC maintained, and kidney EC decreased colony-forming unit-spleen day-8 colonies.
• HSC competitive repopulating activity was preserved with heart and liver EC but lost with kidney EC.

Conclusions:

• Primary EC from nonhematopoietic organs exhibit differential effects on HSC function.
• Heart and liver EC support HSC function ex vivo, while kidney EC impair it.
• These findings suggest organ-specific EC interactions are crucial for maintaining circulating HSC potential.