The Proper Criteria for Identification and Sorting of Very Small Embryonic-Like Stem Cells, and Some Nomenclature Issues

Abstract

Evidence has accumulated that both murine and human adult tissues contain early-development stem cells with a broader differentiation potential than other adult monopotent stem cells. These cells, being pluripotent or multipotent, exist at different levels of specification and most likely represent overlapping populations of cells that, depending on the isolation strategy, ex vivo expansion protocol, and markers employed for their identification, have been given different names. In this review, we will discuss a population of very small embryonic-like stem cells (VSELs) in the context of other stem cells that express pluripotent/multipotent markers isolated from adult tissues as well as review the most current, validated working criteria on how to properly identify and isolate these very rare cells. VSELs have been successfully purified in several laboratories; however, a few have failed to isolate them, which has raised some unnecessary controversy in the field. Therefore, in this short review, we will address the most important reasons that some investigators have experienced problems in isolating these very rare cells and discuss some still unresolved challenges which should be overcome before these cells can be widely employed in the clinic.

Hematopoietic Stem/Progenitor Cells Express Several Functional Sex Hormone Receptors—Novel Evidence for a Potential Developmental Link Between Hematopoiesis and Primordial Germ Cells

“…Specifically, as proposed by some investigators, HSPCs could become specified from a population of migrating PGCs during embryogenesis [7]. In support of this intriguing possibility, HSPCs and PGCs are highly migratory cells, and specification of the first primitive HSPCs in yolk sac blood islands as well as the origin of definitive HSPCs in the aortagonad-mesonephros (AGM) region is chronologically and anatomically correlated with the developmental migration of PGCs in extra-and intra-embryonic tissues [5,6,11]. Furthermore, several papers have described the sharing of chromosomal aberrations between germline tumors and leukemias or lymphomas, which suggests their shared clonal origin [12][13][14][15].…”

“…Furthermore, the recent heated debate about the existence of developmentally early stem cells with broader specification in murine BM has challenged the established hierarchy within the stem cell compartment [5,6]. The responsiveness of HSPCs to SexHs may support the challenging concept of a developmental link between primordial germ cells (PGCs) and hematopoiesis [5][6][7][8][9][10][11].…”

“…The responsiveness of HSPCs to SexHs may support the challenging concept of a developmental link between primordial germ cells (PGCs) and hematopoiesis [5][6][7][8][9][10][11]. Specifically, as proposed by some investigators, HSPCs could become specified from a population of migrating PGCs during embryogenesis [7].…”

Human and Murine Very Small Embryonic-Like Cells Represent Multipotent Tissue Progenitors, In Vitro and In Vivo

“…Given that several independent groups can isolate VSEL cells and have confirmed the in vitro differentiation data [18,[31][32][33], we believe that the reasons for the differences in experimental results are of a technical nature. These differences that are outlined in great detail in a recent publication are most likely due to inadequate isolation procedures [34][35][36]. Nevertheless, some of the critiques of the VSEL cell field are valid; more systematic studies are needed.…”

Very Small Embryonic-Like Stem Cells: A Scientific Debate?

“…From my earliest association with the journal, we have published reports on cell populations isolated from adult tissues that share properties that we routinely associate with cells derived from the inner cell mass of the embryo. Readers interested in tracking these publications are more than welcome to do so, and indeed, the ''issues in development'' piece submitted by the Ratajczak group [1] will give you a helpful list of the keywords necessary to locate these pieces, including the multilineage-differentiating stress-enduring cells reported in this issue [2].…”