Stem Cells Dev. 2017 Jun 5. doi: 10.1089/scd.2017.0012. [Epub ahead of print]

A novel method for the isolation of pluripotent stem cells from human umbilical cord blood.

Monti M¹, Imberti B², Bianchi N³, Pezzotta A⁴, Morigi M⁵, Del Fante C⁶, Redi CA⁷, Perotti C⁸.

Abstract

Very Small Embryonic-Like cells (VSELs) are a population of very rare pluripotent stem cells isolated in adult murine bone marrow and many other tissues and organs, including umbilical cord blood. VSELs existence is still not universally accepted by the scientific community so, on this purpose, we sought to investigate whether presumptive VSELs (pVSELs) could be isolated from human umbilical cord blood with an improved protocol based on the isolation of enriched progenitor cells by depletion of non-progenitor cells with magnetic separation. Progenitor cells, likely including VSELs, cultured with retinoic acid were able to form dense colonies and cystic embryoid bodies and to differentiate towards the ecto-meso-endoderm lineages as shown by the positivity to specific markers. VSELs differentiative potential towards mesodermal lineage was further demonstrated in vitro upon the exposure to an established inductive protocol, which induced the acquisition of renal progenitor cell phenotype. VSEL-derived renal progenitors showed regenerative potential in a cisplatin model of acute kidney injury by restoring renal function and tubular structure through induction of proliferation of endogenous renal cells. The data presented here foster the great debate that surrounds VSELs and, more in general the existence of cells endowed with pluripotent features in adult tissues. In fact, the possibility to find and isolate subpopulations of cells that fully fit all the criteria utilized to define pluripotency remains, nowadays, almost unproven. Thus, efforts to better characterize the phenotype of these intriguing cells are crucial to understand their possible applications for regenerative and precision medicine purposes.