Very Small Embryonic-Like Stem Cells A Review of Basic Science, Applications, and Potential Use in Orthopaedics

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Pierdanilo Sanna
Loubna Abdel Hadi
Rene Antonio Rivero-Jimenez
Antonio Alfonso Bencomo-Hernandez
Yasmine Maher Ahmed
Gina Marcela Torres-Zambrano
Yendry Ventura-Carmenate


Very Small Embryonic-like Stem Cells, VSELS, Pluripotent stem cells, Regenerative medicine, Orthopedic


Continuous and growing research studies regarding the clinical applications of the pluripotent or multipo-tent stem cells with their potential to differentiate into three germ layers are very well conducted in regenerative medicine (RM). In this review, we report the recent clinical applications and potential use of very small embryonic-like stem cells (VSELs) in orthopedics. VSELs are nonhematopoietic (CD45 - / Lin -), rare, and very small cells; they were reported as “dormant” cells in the bone marrow (BM), but are also found in cord blood, peripheral blood (PB), and in adult organs. Based on their capability to express markers of pluripotency (such as Oct-4 +/Nanog +/SSEA-1/4+/CXCR4+), it has been hypothesized that these cells could be early deposited during the embryonic development as descendants of epiblast-derived stem cells and perhaps from some primordial germ cells. VSELs can be released or mobilized from the BM to the PB during tissue injury and stress, facilitating the regeneration of damaged tissues. As well as mesenchymal stem cells, 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. VSELs studies will hopefully open new frontiers to better understand their potential that would be relevant for future applications in RM and translational research.

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