Blood-brain barrier promotes differentiation of human fetal neural precursor cells

In the stem cell niche, neural stem cells (NSCs) are in close contact with the specialized blood-brain barrier (BBB) endothelial cells (ECs) that modulate their proliferation and differentiation behavior. NSCs are also an attractive source for cell transplantation and neural tissue repair after central nervous system injury. After systemic grafting, they are confronted with the BBB before they can enter the brain parenchyma. We investigated the interactions of human fetal neural precursor cells (hfNPCs) with human brain ECs in an in vitro model using primary cultures. We demonstrated that hfNPCs efficiently differentiate to neurons, astrocytes, and oligodendrocytes and move to the subendothelial space of human BBB endothelium, but not to pulmonary artery ECs. Effective differentiation was found to be dependent on the chemokine CCL2/MCP-1, but not on CXCL8/IL-8. Our findings suggest that neural precursor cells specifically interact with the BBB endothelium and differentiate in the subendothelial niche into astrocytes, neurons, and oligodendrocytes, under the influence of the chemokine CCL2/MCP-1.