Blood-forming stem cells are nervous: Direct and indirect regulation of immature human CD34+ cells by the nervous system

The nervous system regulates immunity through hormonal and neuronal routes as part of host defense and repair mechanism. Here, we review the emerging evidence for regulation of human hematopoietic stem and progenitor cells (HSPC) by the nervous system both directly and indirectly via their bone marrow (BM) niche-supporting stromal cells. Functional expression of several neurotransmitter receptors was demonstrated on HSPC, mainly on the more primitive CD34+/CD38−/low fraction. The myeloid cytokines, G-CSF and GM-CSF, dynamically upregulate neuronal receptor expression on human HSPC. This is followed by an increased response to neurotransmitters, leading to enhanced proliferation and motility of human CD34+ progenitors, repopulation of the murine BM and their egress to the circulation. Importantly, recent observations showed rapid mobilization of human HSPC to high SDF-1 expressing ischemic tissues of stroke individuals followed by neoangiogenesis, neurological and functional recovery. Along with decreased levels of circulating immature CD34+ cells and SDF-1 blood levels found in patients with early-stage Alzheimer’s disease, these findings suggest a possible involvement of human HSPC in brain homeostasis and thus their potential clinical applications in neuropathology.