“Small Stem Cells” in Adult Tissues: Very Small Embryonic-Like Stem Cells (VSELs) Stand Up!

This review summarizes information regarding the rare population of very small embryonic-like stem cells (VSELs) that has been identified in adult tissues, emphasizing both their unique morphological features and potential biological significance. We focus on their pluripotent nature and expression of markers characteristic for embryonic stem cells (ESCs), epiblast (EP)SCs, and primordial germ cells (PGCs). Furthermore, we will discuss their rank in the developmental hierarchy of the SC compartment as well as their relationship to other bone marrow-derived, primitive, nonhematopoietic SCs including: i) endothelial progenitor cells (EPCs); ii) mesenchymal (M)SCs; iii) multipotent adult progenitor cells (MAPCs); iv) marrow-isolated adult multilineage inducible (MIAMIs) cells; v) multipotent adult (MA)SCs; and vi) OmniCytes. We will also present different populations of very “small SCs” that have been recently described in the literature (e.g., spore-like cells and Lin-/ALDHhigh long-term repopulating hematopoietic SCs).