Cellular Origin of Testis-Derived Pluripotent Stem Cells: A Case for Very Small Embryonic-Like Stem Cells

Abstract

It has been suggested that testicular germ stem cells represent the only adult body stem cells that dedifferentiate and reprogram into a pluripotent state without any genetic modification. Emerging debate about the authenticity of embryonic stem cell (ES)-like cells derived from adult testicular tissue has prompted us to put forth this letter. We wish to reinforce our findings that pluripotent very small embryonic-like stem cells (VSELs) exist as a small population in adult mammalian testis and may result in ES-like colonies. Because of their small size, it is felt that VSELs could be contaminating the initial cells used for seeding, although efforts were made to place a single germ cell per well in a 96-well plate for clonal expansion, or magnetic activated cell sorting (MACS)-sorted α6 integrin positive cells were used. On a similar note, it is felt that the presence of VSELs in various tissues along with mesenchymal stem cells (MSCs) may provide an alternative explanation to the transdifferentiation potential of MSCs. We conclude that like Oct-4 biology, presence of VSELs in adult body tissues has somewhat surprised stem cell biologists.

Very small embryonic-like stem cells as a novel developmental concept and the hierarchy of the stem cell compartment

“…As recently demonstrated by others, these cells are also high up in the mesenchymal lineage hierarchy [8] and give rise to endothelium [35], and lung epithelium [69,70]. Moreover, VSELs isolated from gonads give rise to the female and male gametes [5,[71][72][73]. The corresponding populations of SSEA-4 + /Oct-4 + /CD133 + /CD34 + / CXCR4 + /Lin À /CD45 À cells were also identified by us in human umbilical cord blood (UCB).…”

Human and Murine Very Small Embryonic-Like Cells Represent Multipotent Tissue Progenitors, In Vitro and In Vivo

“…There is no doubt that isolation of VSEL cells and their cultivation is a difficult endeavor. Given that several independent groups can isolate VSEL cells and have confirmed the in vitro differentiation data [18,[31][32][33], we believe that the reasons for the differences in experimental results are of a technical nature. These differences that are outlined in great detail in a recent publication are most likely due to inadequate isolation procedures [34][35][36].…”

Pluripotent Stem Cells in Bone Marrow and Cord Blood

“…The Umbilical Cord Blood (UCB)-purified VSELs have also been reported to differentiate into neural cells [44] and after co-culture over OP-9 stroma cells were specified into HSCs similar to murine BM-derived VSELs [45]. Apart from umbilical cord blood and bone marrow, VSELs have also been reported in Wharton's jelly and gonadal tissue [46][47][48][49][50][51]. Their presence amongst the MSCs in the Wharton's jelly is in agreement with observations made by other groups that MSCs contain a sub-population of more primitive stem cells [52] or even as postulated by Taichman and group [53] that VSELs are precursors of MSCs.…”