Enumeration of very small embryonic-like stem cells in peripheral blood.

In addition to hematopoietic stem and progenitor cells (HSPCs) also other types of stem cells (e.g., -mesenchymal stem cells [MSCs], endothelial progenitor cells [EPCs], and very small embryonic-like stem cells [VSELs]) circulate under steady-state conditions at detectable levels in peripheral blood (PB), with their numbers increasing in response to stress, inflammation, tissue organ injury (e.g., heart infarct, stroke, or colitis), or mobilizing agents (e.g., granulocyte colony-stimulating factor; G-CSF). This mobilization process may be envisioned as a danger-sensing response mechanism triggered by hypoxia or mechanical- or infection-induced tissue damage that recruits into peripheral blood various types of stem cells that play a role not only in immune surveillance but also in organ/tissue regeneration. Thus, stem cells circulating in PB could be envisioned as "cellular paramedics" that are involved in immune surveillance (HSPCs) or -tissue/organ rejuvenation (MSCs, EPCs, VSELs). In this chapter we focus on detection and enumeration of VSELs circulating in human PB, which are circulating in steady-state conditions or after administration of G-CSF or as a consequence of various pathological events.