Continued Investigations of Very Small Embryonic-Like Stem Cells in Adult Tissues

It is important in the development of the present and the next generation of stem cell therapies to have cheap, reliable access to patient-specific pluripotent stem cells on demand. These are the basic starting point for generating therapeutic cells of a specific type, and only pluripotent cells have the capacity to create cells of any type. This is why there there is so much interest in developing the technology of induced pluripotency, for example, by which any cell sample from a patient can be used to create pluripotent cells. Some researchers believe that adult tissues contain populations of pluripotent stem cells necessary to continued tissue maintenance over a lifetime. If the case, these would be a useful source of cells for cell therapies. These proposed cell populations are given various names by various different research groups, such as very small embyronic-like stem cells. There is still some debate over whether such pluripotent cell populations actually exist in adult tissues, and whether researchers are accurately characterizing their observations. Research continues, however:

The pancreas is one of three organs (besides lung and liver) with huge regenerative ability. Mouse pancreas has a remarkable ability to regenerate after partial pancreatectomy, and several investigators have studied the underlying mechanisms involved in this regeneration process; however, the field remains contentious. Elegant lineage-tracing studies undertaken over a decade have generated strong evidence against neogenesis from stem cells and in favor of reduplication of pre-existing islets. Ductal epithelium has also been implicated during regeneration. We recently provided direct evidence for the possible involvement of very small embryonic-like stem cells (VSELs) during regeneration after partial pancreatectomy in mice.

VSELs were first reported in pancreas in 2008 and are mobilized in large numbers after treating mice with streptozotocin and in patients with pancreatic cancer. VSELs can be detected in mouse pancreas as small-sized LIN-/CD45-/SCA-1+ cells (3 to 5 μm), present in small numbers (0.6%), which express nuclear Oct-4 (octamer-binding transcription factor 4) and other pluripotent markers along with their immediate descendant 'progenitors', which are slightly bigger and co-express Oct-4 and PDX-1. VSELs and the progenitors get mobilized in large numbers after partial pancreatectomy and regenerate both pancreatic islets and acinar cells.

In this review, we deliberate upon possible reasons why VSELs have eluded scientists so far. Because of their small size, VSELs are probably unknowingly and inadvertently discarded during processing. Several issues raised in the review require urgent confirmation and thus provide scope for further research before arriving at a consensus on the fundamental role played by VSELs in normal pancreas biology and during regeneration, aging, and cancer. In the future, such understanding may allow manipulation of endogenous VSELs to our advantage in patients.


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