Very small embryonic-like (VSEL) stem cells in adult organs and their potential role in rejuvenation of tissues and longevity

Abstract

Recently, we purified rare CXC chemokine receptor 4 expressing (CXCR4 + ) small stem cells (SCs) from the murine bone marrow (BM) that express markers characteristic for embryonic (E)SCs, epiblast (EP)SCs, and primordial germ cells (PGCs). We named these primitive cells very small embryonic-like (VSEL) SCs (VSELs). Our data indicate that VSELs are also present in many other organs in mice and that they may differentiate into cells from all three germ layers. Similar SCs were also isolated from human cord blood (CB) and mobilized peripheral blood (mPB). We hypothesize that VSELs are deposited during gastrulation and organogenesis in developing organs/tissues of mammals as a population of pluripotent stem cells (PSCs) that give rise to tissue committed monopotent SCs and that their number decreases with age. Therefore VSELs could play a pivotal role in normal rejuvenation of adult tissues as well as involvement in regeneration of damaged organs. Thus, these cells are potential SCs candidates for regenerative medicine and we envision that the regenerative potential of these cells could be harnessed to decelerate the aging processes.

Identification and characterization of putative stem cells in the adult pig ovary

“…4E), indicating their transformation to a differentiating status. Previous investigations showed that Vasa-positive VSEL stem cells isolated from adult organs express several characteristic markers of early PGCs, including fetal-type alkaline phosphatase, Oct4, SSEA-1, CXCR4, Stella, Fragilis, Nobox and Hdac6 (Ratajczak et al, 2008). Because the porcine PSCs described herein similarly express a number of typical, early PGC markers (Figs 2 and 4), these findings might indicate a close association of PSCs with Vasa-positive VSELs and epiblast-derived PGCs.…”

“…These cells expressed early primordial germ cell (PGC) markers, including OCT4 (POU5F1), NANOG and SOX2 (Virant-Klun et al, 2008). The isolated PGCs were similar to cells termed 'very small embryonic-like (VSEL) stem cells', which have been found in a number of human and other animal adult tissues (Ratajczak et al, 2008).…”

Potentiality of Very Small Embryonic-Like Stem Cells to Repair Myocardial Infarction

“…Especially, not only a number of these cells in adult organs decreases with the age but also their ability to form spheres containing VSEL-DS declaims with time. Whereas, a number of monopotent hemato/lymphopoiesis committed HSC increase in older animals [40,41].This age-dependent content and ability of VSELs in adult organs may explain that these cells could play a pivotal role in the normal cell turn over and the life span control of mammals.Moreover, a significantly higher number of VSELs in long-living murine strains (e.g., Laron dwarfs and Ames dwarfs), whose longevity is explained by low levels of circulating IGF1 and a decrease in IIS. By contrast, the number of VSELs is reduced in mice with high levels of circulating IGF1 and enhanced IIS (e.g., growth hormone-overexpressing transgenic mice) compared to normally aging littermates [42,43].…”

“…Thus, VSELs may be progeny of epiblast cells to develope tissues and a reserve pool of PSCs to repair tissue. Furthermore, the quiescent state of VSELs may also be a physiological protective mechanism of preventing uncontrolled proliferation, tumor formation [28]. Furthermore, The bone-forming activity of VSELs, exceeded the activity of other populations of BM-purified cells tested in the same assay if embedded in gelatin sponges and implanted into living mice.…”

“…Interestingly, VSELs are somewhat heterogenous developmentally. Although all of VSELs express the Oct-4, some of them express genes that are more closely related to genes expressed by EP-SCs and others to genes expressed by migrating PGCs [28].…”