VSELs

BACKGROUND

Both pluripotent very small embryonic-like stem cells (VSELs) and induced pluripotent stem (iPS) cells were reported in 2006. In 2012, a Nobel Prize was awarded for iPS technology. The VSELs maintain life-long tissue homeostasis, serve as a backup pool for adult stem cells and are mobilized under stress conditions.

In this context it is hypothesized that VSELs are epiblast- derived PSCs that are deposited in developing organ/tissues as a population of stem cells that gives origin to mono-potent tissue committed stem cells. Mono-potent stem cells that are already committed to particular organs/tissues.

Evidence indicates that VSELs are:

  1. A population of migratory cells, and their number increases both in mice and in humans in PB during stress situations related to tissue or organ injuries (e.g., heart infarct, stroke, skin burns, or acute colitis).
  2. These cells, which are mobilized into PB (Peripheral Blood) where they then circulate, may play a physiologically important surveillance role in repairing minor tissue damage.
  3. The elevated number of VSELs observed in UCB may be explained as a physiological mechanism in which these cells are mobilized in newborns, which, because of hypoxia and delivery stress, experience numerous minor tissue injuries.
  4. Thus, the mobilization of VSELs into UCB is an inborn protective mechanism, which “can be considered as the original physiological SC therapy,” that everybody experiences in life after delivery.
  5. The number of VSELs circulating in PB also increases after administration of certain drugs that are used on a routine basis in the clinic to mobilize HSCs into PB (eg, G-CSF [granulocyte-colony stimulating factor] or AMD3100 [Plerixafor, Mozobil]) for bone marrow Transplantation. Thus, VSELs could be harvested for potential clinical applications, like HSCs from mPB, by using similar protocols for leukapheresis.
  6. The problem of low recovery of these cells from BM, UCB, and mPB is ameliorated by a recently established ex vivo expansion protocol for these cells.
  7. Their embryonic-like characteristics include the expression of markers of pluripotency; the ability to give rise to cellular derivatives of all three germ-layers; and the ability to form embryoid-like bodies. Indeed, quiescent VSELs may represent the remnants of epiblast-derived cells in adult organs.
  8. Given the ability of VSELs to differentiate into cardiomyocytes and endothelial cells, and their ability to secrete various cardioprotective growth factors/cytokines, VSELs may serve as an ideal cellular source for cardiac repair. Consistently, transplantation of VSELs after an acute MI improves left ventricular (LV) structure and function, and these benefits remain stable during long-term follow-up.
  9. After tissue injury, including acute myocardial infarction (MI), bone marrow–derived VSELs are mobilized into the peripheral blood and home to the damaged organ. Although the mechanisms remain under investigation, effects of secreted factors, regeneration of cellular constituents, and stimulation of endogenous stem/progenitors may play combinatorial roles.