Human Umbilical Cord Blood-Derived Very-Small-Embryonic-Like Stem Cells with Maximum Regenerative Potential?

I read with interest the recent article by Bhartiya claiming that the small Oct-4+ cells (called very small embryonic-like stem cells [VSELs]) were discarded during Ficoll-Hipaque processing of cord blood [1]. In fact, this article could be an interesting technical notice. However, there are lots of statements in this article that are difficult to accept.

What is the experimental basis of the statement that human cord blood-derived VSELs are pluripotent stem cells with a maximum regenerative potential? Apart from some data demonstrating that umbilical cord blood (UCB)-VSELs, after a co-culture with stromal cells, could generate the cells that are able to establish a lympho-hematopoietic chimerism in NOD/Scid mice [2] (to be confirmed), what are the other arguments?

Until now, a stem cell entity was defined on the basis of its functional properties: differentiation potential and self-renewal capacity. In practice, a stem cell exhibits a high proliferative capacity and is able to regenerate the various cell lines from a tissue (such as hematopoietic stem cell) or two or more tissues. Thus, one cell could deserve a stem cell title on the basis of what it is able to do, not what it looks like. In that respect, the pluripotent nature of VSELs could be judged and proved only on the basis of their potential to differentiate into functional cells of all tissues (meaning of term “pluripotent”). However, the authors state: “Multi-parametric analysis was employed to characterize and confirm the pluripotent nature of the VSELs by visualizing morphology and their Hoffman optics H&E staining, immunolocalization for pluripotent germ cell and hematopoietic markers and QPCR” [1]. How, on the basis of these analyses, could one characterize and confirm pluripotent nature of stem cells?

Reading carefully this article, either I do not understand these and similar statements or they are fundamentally incorrect. Either native (isolated starting from the mononuclear cell fraction obtained on the Ficoll gradient) or ex vivo-expanded CD34+ cells from cord blood are capable of long-term reconstitution of the hematopoietic system [3,4]. Processed [5,6] and banked cord blood cells are transplanted in allogeneic context on a daily basis [7], providing lifelong lympho-hematopoietic reconstitutions of patients. On the contrary, there is not enough experience to conclude anything concerning the autologous UCB transplantation. So, I do not see how “the results of the present study may help explain low efficacy reported during adult autologous stem cells trials,….”

Finally, the concluding paragraph at the end of the discussion is neither related to the results presented in article nor supported by literature data relevant for the stem cell function.