Very Small Embryonic Like Stem Cells: A Review of Basic Science, Applications, and Potential Use in Orthopedics |Biomedgrid

Research studies designed to show the clinical efficacy of the Pluripotent/Multipotent Stem Cells to differentiate into three germ layers have been conducted in the context of Regenerative Medicine (RM). This review describes recent clinical applications and the potential use of Very Small Embryonic-like Stem Cells (VSELs) in the context of orthopedic problems such as degenerative joint disease. VSELs are non-hematopoietic (Lin-/ CD45-), rare, and quiescent cells; they were reported to be “dormant” cells in the Bone Marrow (BM). However, they are now found in cord blood, Peripheral Blood (PB), and other organs. Their positive expression of pluripotency markers, such as Oct‐4+/Nanog+/SSEA-1/4+/CXCR4+, has been used to hypothesize that these cells could be deposited early during embryonic development as descendants of epiblast‐derived stem cells, and perhaps from a more primordial germ cell. VSELs can be released/mobilized from the BM to the PB during tissue injury and stress, facilitating the regeneration of damaged tissues and stimulation of mesenchymal stem cells to divide/differentiate. Nowadays, VSELs can be expanded ex vivo. Their pluripotency could be suitable for applications in RM, solving several problems regarding the use of both controversial embryonic stem cells and induced pluripotent stem cells. Additional studies on VSELs and their characterization will provide a better understanding of their biological and regenerative potential for future clinical applications in orthopedics.