A population of very small embryonic-like (VSEL) CXCR4+SSEA-1+Oct-4+ stem cells identified in adult bone marrow

Abstract

By employing multiparameter sorting, we identified in murine bone marrow (BM) a homogenous population of rare (B0.02% of BMMNC) Sca-1 þ lin À CD45 À cells that express by RQ-PCR and immunohistochemistry markers of pluripotent stem cells (PSC) such as SSEA-1, Oct-4, Nanog and Rex-1. The direct electronmicroscopical analysis revealed that these cells are small (B2-4 lm), posses large nuclei surrounded by a narrow rim of cytoplasm, and contain open-type chromatin (euchromatin) that is typical for embryonic stem cells. In vitro cultures these cells are able to differentiate into all three germ-layer lineages. The number of these cells is highest in BM from young (B1-monthold) mice and decreases with age. It is also significantly diminished in short living DBA/2J mice as compared to long living B6 animals. These cells in vitro respond strongly to SDF-1, HGF/SF and LIF and express CXCR4, c-met and LIF-R, respectively, and since they adhere to fibroblasts they may be coisolated with BM adherent cells. We hypothesize that this population of Sca-1 þ lin À CD45 À very small embryonic-like (VSEL) stem cells is deposited early during development in BM and could be a source of pluripotent stem cells for tissue/ organ regeneration.

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

“…We named these primitive cells very small embryonic-like (VSEL) SCs (VSELs). Our data indicate that VSELs may differentiate into cells from all three germ layers (Kucia et al, 2006a). The number of these cells is high in young mice and decreases with the age.…”

“…Generally, HSCs and other non-HSCs are actively chemoattracted by factors secreted by BM stroma cells and osteoblasts [e.g., stromal derived factor-1 (SDF-1), hepatocyte growth factor (HGF), and/or vascular endothelial growth factor (VEGF)] and colonize marrow by the end of the second and the beginning of the third trimester of gestation (Nagasawa, 2000). We envision that all these non-HSCs residing in the BM (e.g., VSELs) have some role in the homeostasis and turnover of peripheral tissues and, if needed, could be mobilized from the BM into circulation during tissue injury and stress (Figure 1 panel B), thereby facilitating the regeneration of damaged organs (Kollet et al, 2003;Kucia et al, 2004;Kucia et al, 2006a;Kucia et al, 2006b;Kucia et al, 2006c, Kucia et al 2008. Table II lists different types of non-HSCs that have been postulated to reside in BM tissue.…”

“…VSEL SCs as determined by RQ-PCR by employing specific primers and by immunohistochemistry markers of PSCs such as SSEA-1, Oct-4, Nanog, and Rex-1 as well as Rif-1 telomerase protein (Kucia et al, 2006a). …”

“…Recently, we purified rare, small CXC chemokine receptor 4 expressing (CXCR4 + ) SCs from the murine BM and several adult organs in mice that express markers characteristic for embryonic (E)SCs, epiblast (EP)SCs, and primordial (P)GCs (Kucia et al, 2006a). We named these primitive cells very small embryonic-like (VSEL) SCs (VSELs).…”

Where new approaches can stem from: Focus on stem cell identification

“…However, 2 years ago a unique adult pluripotent stem cell population, the very small embryonic-like stem cells (VSELs) were discovered in murine bone marrow (6) and have consequently become the subject of investigation in various other murine and human tissues as well. They have now been detected in several adult organs of the mouse and the data being covered in a recent Rapid Publication of the journal (7).They are further characterized in this focus issue in the context of other ''small stem cell'' populations described in the literature (8).…”