Very Small Embryonic-Like Stem Cells A Review of Basic Science, Applications, and Potential Use in Orthopaedics
Main Article Content
Keywords
Very Small Embryonic-like Stem Cells, VSELS, Pluripotent stem cells, Regenerative medicine, Orthopedic
Abstract
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.
References
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14. Bhartiya D. Will iPS cells regenerate or just provide trophic support to the diseased tissues? Stem Cell Rev. 2018;14:629–31. https://doi.org/10.1007/s12015-018-9837-6
15. Kanji S, Pompili VJ, Das H. Plasticity and maintenance of hematopoietic stem cells during development. Recent Pat Biotechnol. 2011;5(1):40–53. https://doi.org/10.2174/187220811795655896
16. Alison MR, Poulsom R, Jeffery R, et al. Hepatocytes from non-hepatic adult stem cells. Nature. 2000;406(6793):257. https://doi.org/10.1038/35018642
17. Petersen BE, Bowen WC, Patrene KD, et al. Bone marrow as a potential source of hepatic oval cells. Science. 1999;284(5417):1168–70. https://doi.org/10.1126/science.284.5417.1168
18. Ferrari G, Cusella-De Angelis G, Coletta M, et al. Muscle regeneration by bone marrow-derived myogenic progenitors [published correction appears in Science. 1998;281(5379):923]. Science. 1998;279(5356):1528–30.
19. Gussoni E, Soneoka Y, Strickland CD, et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature. 1999;401(6751):390–4. https://doi.org/10.1038/43919
20. Saw KY, Anz A, Siew-Yoke Jee C, et al. Articular cartilage regeneration with autologous peripheral blood stem cells versus hyaluronic acid: A randomized controlled trial. Arthroscopy. 2013;29(4):684–94. https://doi.org/10.1016/j.arthro.2012.12.008
21. Mezey E, Chandross KJ, Harta G, Maki RA, McKercher SR. Turning blood into brain: Cells bearing neuronal antigens generated in vivo from bone marrow. Science. 2000;290:1779–82. https://doi.org/10.1126/science.290.5497.1779
22. Brazelton TR, Rossi FM, Keshet GI, Blau HM. From marrow to brain: Expression of neuronal phenotypes in adult mice. Science. 2000;290:1775–9. https://doi.org/10.1126/science.290.5497.1775
23. Asahara T, Masuda H, Takahashi T, et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res. 1999;85(3):221–8. https://doi.org/10.1161/01.res.85.3.221
24. Bittner RE, Schöfer C, Weipoltshammer K, et al. Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anat Embryol (Berl). 1999;199(5):391–6. https://doi.org/10.1007/s004290050237
25. Orlic D, Kajstura J, Chimenti S, Bodine DM, Leri A, Anversa P. Transplanted adult bone marrow cells repair myocardial infarcts in mice. Ann N Y Acad Sci. 2001;938:221–9. https://doi.org/10.1111/j.1749-6632.2001.tb03592.x
26. Kucia M, Reca R, Campbell FR, et al. A population of very small embryonic-like (VSEL) CXCR4(+) SSEA-1(+) Oct-4+ stem cells identified in adult bone marrow. Leukemia. 2006;20(5):857–69. https://doi.org/10.1038/sj.leu.2404171
27. Bhartiya D. Pluripotent stem cells in adult tissues: Struggling to be acknowledged over two decades. Stem Cell Rev. 2017;13:713–24. https://doi.org/10.1007/s12015-017-9756-y
28. Kucia M, Reca R, Jala VR, Dawn B, Ratajczak J, Ratajczak MZ. Bone marrow as a home of heterogenous populations of nonhematopoietic stem cells. Leukemia. 2005;19(7):1118–27. https://doi.org/10.1038/sj.leu.2403796
29. Eglitis MA, Mezey E. Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci U S A. 1997;94(8):4080–5. https://doi.org/10.1073/pnas.94.8.4080
30. Kucia M, Wu W, Ratajczak MZ. Bone marrow-derived very small embryonic-like stem cells: Their developmental origin and biological significance. Dev Dyn. 2007;236(12):3309–20. https://doi.org/10.1002/dvdy.21180
31. Kmiecik TE, Keller JR, Rosen E, Vande Woude GF. Hepatocyte growth factor is a synergistic factor for the growth of hematopoietic progenitor cells. Blood. 1992;80(10):2454–7.
32. Nagasawa T. A chemokine, SDF-1/PBSF, and its receptor, CXC chemokine receptor 4, as mediators of hematopoiesis. Int J Hematol. 2000;72(4):408–11.
33. Taichman R, Reilly M, Verma R, Ehrenman K, Emerson S. Hepatocyte growth factor is secreted by osteoblasts and cooperatively permits the survival of haematopoietic progenitors. Br J Haematol. 2001;112(2):438–48. https://doi.org/10.1046/j.1365-2141.2001.02568.x
34. Shin DM, Suszynska M, Mierzejewska K, Ratajczak J, Ratajczak MZ. Very small embryonic-like stem-cell optimization of isolation protocols: An update of molecular signatures and a review of current in vivo applications. Exp Mol Med. 2013;45(11):e56. https://doi.org/10.1038/emm.2013.117
35. Kucia M, Halasa M, Wysoczynski M, et al. Morphological and molecular characterization of novel population of CXCR4+ SSEA-4+ Oct-4+ very small embryonic-like cells purified from human cord blood: Preliminary report. Leukemia. 2007;21(2):297–303. https://doi.org/10.1038/sj.leu.2404470
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May 9, 2023
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Sanna, P., Abdel Hadi, L., Rivero-Jimenez, R. A., Bencomo-Hernandez, A. A., Maher Ahmed, Y., Torres-Zambrano, G. M., & Ventura-Carmenate, Y. (2023). Very Small Embryonic-Like Stem Cells: A Review of Basic Science, Applications, and Potential Use in Orthopaedics. Biologic Orthopedics Journal, 5(1), e1-e11. https://doi.org/10.22374/boj.v5i1.30
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