The Treasury of Wharton's Jelly

Abstract

Background Postnatal umbilical cord tissue contains valuable mesenchymal progenitor cells of various differentiation stages. While mesenchymal stem cells are plastic-adherent and tend to differentiate into myofibroblastic phenotypes, some round cells detach, float above the adherent cells, and build up cell aggregates, or form spheroids spontaneously. Very small luminescent cells are always involved as single cells or within collective forms and resemble the common well-known very small embryonic-like cells (VSELs). In this study, we investigated these VSELs-like cells in terms of their pluripotency phenotype and tri-lineage differentiation potential. Methods VSELs-like cells were isolated from cell-culture supernatants by a process that combines filtering, up concentration, and centrifugation. To determine their pluripotency character, we measured the expression of Nanog, Sox-2, Oct-4, SSEA-1, CXCR4, SSEA-4 on gene and protein level. In addition, the cultured cells derived from UC tissue were examined regarding their potential to differentiate into three germ layers. Result The VSELs-like cells express all of the pluripotency-associated markers we investigated and are able to differentiate into meso- endo- and ectodermal precursor cells. Conclusions Umbilical cord tissue hosts highly potent VSELs-like stem cells. Graphical Abstract

In Vitro Simulated Neuronal Environmental Conditions Qualify Umbilical Cord Derived Highly Potent Stem Cells for Neuronal Differentiation

“…These data indicated that they could be indeed developmentally related to a population of migrating epiblast-derived PGCs [ 43 ]. In addition, like other research groups before us, we were able to show that VSEL-like cells have the ability to differentiate into stem cells of three different germ layers [ 16 , 44 ]. In this context it could be demonstrated that murine or human VSEL like cells were differentiable into neuron marker expressing cells in vitro [ 45 ] and in vivo [ 46 ].…”

“…The most common view is that cells of mesodermal tissues such as the UC can acquire properties of ectodermal cells by transdifferentiation and thereby become differentiable into neuronal cells [ 36 ]. Here we focus rather on the pluripotent stem cell fraction of the UC which were already discovered in our last study [ 16 ]. This pluripotent stem cell fraction consists of tiny roundish stem cells that were seen as single cells directly attached to large adherent stromal cells that were attached to the plastic.…”

“…According to our previous study, we demonstrate that a small portion of UC-MSCs behave other than typical MSCs, as these cells show no plastic adherence but spontaneously form spheroids and show pluripotent characteristics [ 16 ]. With this study we go one step further and demonstrate that UC-MSCs derived SCSs, are comprised of highly potent cells that gain neuronal functionality after simultaneous neuro-mechanotransductive and neuro-biochemical stimulation.…”

In Vitro Profiling of Application Ready Human Surrogate Primary Progenitor Stromal Cell Fractions

“…A comprehensive analysis of embryonic stem cell line and bone marrow-derived MSCs did demonstrate great similarities in their cellular genetic and proteomic profiles [28]. Our study was inspired in part by a recently conducted analysis of cultured in vitro cell based system while the aim of our study was to characterize biological discard derived primary progenitor stromal cells, sorted cells and CNC, to leverage their signature features in developing application ready in vitro human surrogate microphysiological systems [29].…”

“…In other words, we configured it by enriching the cellular population with the SSEA4 cells (30-72%) and further culture expanding them. Cells bearing this marker are known to have the capacity for triploblastic differentiation into three germ layers and selfrenewal [29]. The identification of SSEA4 positive cells from human tissue has precedence; SSEA4-positive cells have been previously identified from several human tissues like human fetal forebrain, forebrain-derived neurosphere cells, and human adult ovaries [31].…”