Even though many stem cells researchers do not believe that they exist, Very Small Embryonic-Like (VSELs) Stem Cells from bone marrow have continued to be a subject of research. A recent paper in the journal Stem Cells and Development by Russ Taichman (University of Michigan) and colleagues has documented, for this first time, that VSELs from mice and humans are multipotent (that is, able to differentiate into several different mature, adult cell types) when transplanted into a living animal.
VSELs are very rare, very small embryonic-like stem cells. They represent a rare population in the bone marrow (less than 0.02% of nucleated cells), but have been identified in most tissues that have been examined, including blood and other solid organs (see Kucia M, J Ratajczak, R Reca, A Janowska-Wieczorek and MZ Ratajczak. (2004). Tissue-specific muscle, neural and liver stem/progenitor cells reside in the bone marrow, respond to an SDF-1 gradient and are mobilized into peripheral blood during stress and tissue injury. Blood Cells Mol Dis 32:52–57).
Because VSELs express some of the same genes that are expressed in human embryonic stem cells (e.g., Oct4, nanog, and stage-specific embryonic antigen or SSEA-1), there is a hope that they can differentiate into cell types from all three embryonic germ layers.
When Taichman and his colleagues implanted human VSELs into mice that had suffer skull injuries, the cells produced robust mineralized tissue that came from human cells. When this mineralized material was examined in more detail, it was clear that the human VSELS had formed neurons, adipocytes (fat cells), chondrocytes (cartilage cells), and osteoblasts (bone cells) within the skull lesions.
The ability of these most-primitive, multipotent stem cells to differentiate into bone, neurons, connective tissue, and other cell types, was also accompanied by a protocol that contained the proper criteria for identifying and isolating VSELs. A second paper that tends to corroborate Taichman’s work was also published in the same volume of Stem Cells and Development.
Malwina Suszynska and others from the University of Louisville, KY, and Pomeranian Medical University (Szczecin) and Jagiellonian University (Krakow), Poland explores the challenges involved with isolating these rare stem cells and the importance of not confusing VSELs with other types of stem cells. In their article, “The Proper Criteria for Identification and Sorting of Very Small Embryonic-Like Stem Cells (VSELs), and Some Nomenclature Issues,” the authors present the most current descriptions and terminology for characterizing VSELs.
“I find the data presented by the Taichman group to be compelling and challenging. However, the current debate as to the significance of the body of publications concerning VSELs can only be resolved by a cooperative investigation across laboratories using identical methodologies and source materials,” says Editor-in-Chief Graham C. Parker, PhD, The Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI.
The significance of these papers is potentially huge. When Irving Weissman’s laboratory was unable to isolate and demonstrate the existence of VSELs, others who had also failed to find these rare cells wrote VSELs off as a figment of particular researchers imagination. These two new papers, however, provide a detailed protocol with specific criteria for identifying these cells. If other groups can get these protocols to work, then VSELs should be regarded as vindicated. However, if no one else except the insular VSEL research group can get these protocols to work, then I think skepticism is still warranted.
I will reiterate my original suggestions: Researchers from the Weissman and Alt laboratories should visit these other laboratories and learn how to isolate VSELs from the people who actually do it. If they cannot get these protocols to work on their own laboratories, or if there is evidence of impropriety or incompetence, then skepticism of the existence of VSELs will certainly be vindicated. However, if these techniques can be learned and made to work in other laboratories, then I think we should be comfortable with the existence of VSELs.