Very small embryonic-like stem cells (VSELs) represent a real challenge in stem cell biology: recent pros and cons in the midst of a lively debate

Abstract

The concept that adult tissue, including bone marrow (BM), contains early-development cells with broader differentiation potential has again been recently challenged. In response, we would like to review the accumulated evidence from several independent laboratories that adult tissues, including BM, harbor a population of very rare stem cells that may cross germ layers in their differentiation potential. Thus, the BM stem cell compartment hierarchy needs to be revisited. These dormant, early-development cells that our group described as very small embryonic-like stem cells (VSELs) most likely overlap with similar populations of stem cells that have been identified in adult tissues by other investigators as the result of various experimental strategies and have been given various names. As reported, murine VSELs have some pluripotent stem cell characteristics. Moreover, they display several epiblast/germline markers that suggest their embryonic origin and developmental deposition in adult BM. Moreover, at the molecular level, changes in expression of parentally imprinted genes (for example, Igf2–H19) and resistance to insulin/insulin-like growth factor signaling (IIS) regulates their quiescent state in adult tissues. In several emergency situations related to organ damage, VSELs can be activated and mobilized into peripheral blood, and in appropriate animal models they contribute to tissue organ/regeneration. Interestingly, their number correlates with lifespan in mice, and they may also be involved in some malignancies. VSELs have been successfully isolated in several laboratories; however, some investigators experience problems with their isolation.

FSH–FSHR3–stem cells in ovary surface epithelium: basis for adult ovarian biology, failure, aging, and cancer

“…However, owing to their very small size (smaller than red blood cells), VSELs have remained obscure, controversial, and poorly studied till date (Abbott 2013, Ratajczak et al 2014. Emerging literature suggests that VSELs do exist and similar to mouse bone marrow VSELs that survive total body irradiation (Ratajczak et al 2011), we have observed that both adult mouse testicular (Anand et al 2014) and ovarian VSELs survive chemotherapy (Fig.…”

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.…”

Untitled

“…13,14 In this study, VSELs were cultured on a C2C12 feeder layer that inhibited spontaneous differentiation of VSELs by a signaling pathway and induced VSELs to grow new embryoniclike bodies. 2,9,13 The VSELs can migrate naturally from bone marrow to other tissues and be incorporated with regeneration of injured tissues. 15 The CXCR4 receptors of VSELs may facilitate the migration of these cells to the injured site, as observed with our histologic evidence.…”