• Preclinical and clinical application of Very Small Embryonic Like (VSEL) Stem Cells in Adult tissues
  • Mahsa Rahgoshay,1,* Amir Atashi,2 Mansoureh Ajami,3 Fatemeh Jamshidi,4
    1. Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran
    2. Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Shahroud University of Medical Sciences, Shahroud, Iran
    3. Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Shahroud University of Medical Sciences, Shahroud, Iran
    4. Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran


  • Introduction: In recent years, stem cell-based therapy became a central focus of interest for their application toward regenerative medicine both from ethical and scientific points of view. Thus, an urgent need is felt for an ethical, reliable, and non-controversial source of stem cells to be established as therapeutics. It has been suggested that a new stem cell population, namely, very small embryonic-like stem cells (VSELs) could potentially provide such a therapeutic alternative to the still controversial application of embryonic stem cells (ESC). VSELs represent a rare homogeneous and highly quiescent population, characterized by their very small size and as being CD34+/CD133+/CXCR4+/Lin−/CD45−. The most important feature is that they demonstrate the ability to differentiate into cells from all three germ layers. Moreover, they express pluripotent) Oct-4, NANOG, and Sox2(as well as an embryonic stem cell (SSEA-4, TRA-1-81) specific markers on their surface. Currently, VSELs have been detected in different adult mouse and human tissues and can be mobilized from the bone marrow into the PB in response to tissue injury including stroke, Acute myocardial infarction (AMI), burn injury, Spinal cord injury, hypoxia or critical leg ischemia. Numerous investigations have already been carried out for murine VSELs, only a few for human VSELs, and all the data have been shown that VSELs can participate in various tissue and organ repair such as the brain, liver, lung, kidney as well as heart and could play an encouraging role in aging.
  • Methods: Dawn et al. found that at 35 days after MI, VSEL-treated mice had better global left ventricular (LV) systolic performance and reduced myocyte hypertrophy in surviving tissue compared with controls. Moreover, in a study performed by Zuba-Surma et al. VSELs expanded in culture and exposed to a mixture of cardiomyogenic cytokines and growth factors and retain the ability to alleviate LV dysfunction and remodeling after reperfused MI. Anand et al. revealed that VSELs that survive busulphan treatment could potentially regenerate chemoablated mouse testis when healthy niche cells are transplanted via the intertubular route into the testicular interstitium. Other in vivo experimental models have revealed that transplantation of VSELs could contribute to hepatic and pancreas regeneration as well as hematopoiesis, angiogenesis, and osteogenesis. A recent study demonstrated the involvement of VSELs in the regeneration of mouse bone marrow after 5-fluorouracil treatment.
  • Results: A phase I non-randomized clinical trial data showed that human VSELs triggered post-ischemic revascularization in immunodeficient mice and acquire an endothelial phenotype both in vitro and in vivo. Moreover, the REGENT-VSEL trial sub-analysis demonstrated that transendocardial injection of autologous BM-derived CD133+ stem cells in patients with chronic refractory angina did not show significant improvement in quality of life in comparison to the control group.
  • Conclusion: Finally, VSELs isolated from adult tissues appear to be “true” pluripotent stem cells, which could be used, through their progeny, to regenerate damaged organs, and which may solve the problems inherent in the use of controversial embryonic stem cells or induced pluripotent stem cells (iPSCs). These pluripotent stem cells are autologous, embryo-free, patient-specific, and potentially safe for regenerative medicine with no associated sensitive ethical issues as compared to embryonic stem cells.
  • Keywords: Very small embryonic like stem cells, Stem cells, regenerative medicine