Working With Very Small Embryonic-Like Stem Cells

The existence of very small embryonic-like cells (VSELs) is debated, as while several groups have claimed to isolate them from adult tissues over the past few years, others have failed to replicate this work. There have been some suggestions that these cells might be created in response to specific stresses - which may or may not be present in a researcher's approach to isolating them - rather than lying dormant in all adult tissues. This is important because if VSELs can be reliably obtained from tissues such as skin they will provide a ready, low-cost source of pluripotent cells for research and therapeutic use.

Here is an open access paper published by another group of researchers who are investigating VSELs and their potential utility for future therapies:

The purpose of this study was to determine the lineage progression of human and murine very small embryonic-like (HuVSEL or MuVSEL) cells in vitro and in vivo. VSEL cells represent a rare population in the bone marrow (less than 0.02% of nucleated cells). VSEL cells have been identified in most tissues that have been examined, including blood and other solid organs. VSEL cells have scant cytoplasm and, as the name suggests, have morphologic characteristics indicative of an immature state of differentiation, including dispersed chromatin. In addition, VSEL cells express genes that are expressed by embryonic stem cells, including Oct4, nanog, and stage-specific embryonic antigen SSEA-1. Thus, VSEL cells may give rise to derivatives of all three germ layers. VSEL cells may therefore be prime candidates for cells with the capacity to regenerate many different structures.

In vitro, HuVSEL and MuVSEL cells differentiated into cells of all three embryonic germ layers. HuVSEL cells produced robust mineralized tissue of human origin. Immunohistochemistry demonstrated that the HuVSEL cells gave rise to neurons, adipocytes, chondrocytes, and osteoblasts. MuVSEL cells were also able to differentiate into similar lineages. First round serial transplants of MuVSEL cells demonstrated that 60% of the cells maintained their VSEL cell phenotype while other cells differentiated into multiple tissues at 3 months. Secondary transplants did not identify donor VSEL cells, suggesting limited self renewal but did demonstrate VSEL cell derivatives in situ for up to 1 year. At no point were teratomas identified.

These studies show that VSEL cells produce multiple cellular structures in vivo and in vitro and lay the foundation for future cell-based regenerative therapies for bone, neural, and connective tissue disorders.



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