Repeatability In Question
Most critically, the research has thus far failed to meet criteria of repeatability in a well-known stem cell laboratory. Stanford University School of Medicine’s Irving L. Weissman, M.D., director of the Stanford Institute of Stem Cell Biology and Regenerative Medicine, said, “We found that every step of the way, we could not confirm the results of the Ratajczak group.”
In a nutshell, the Stanford investigators noted that they could not “find VSELs in mouse BM with any of the reported stem cell potentials, specifically for hematopoiesis. We found that: (1) most events within the ‘VSEL’ flow-cytometry gate had little DNA, and the cells corresponding to these events (2) could not form spheres, (3) did not express Oct4, and (4) could not differentiate into blood cells. These results provide a failure to confirm the existence of pluripotent VSELs.”
“Weissman’s evidence is a clincher—it is the end of the road for VSELs,” said Rüdiger Alt, head of research at Vita 34, a private bank for umbilical cord blood in Leipzig, Germany, who published research results last year that described the first failure to replicate claims for the cells.
Robin Smith, M.D., chairman and CEO at NeoStem, disagreed and compared the attacks on VSELs to setbacks suffered by Charles Darwin and Nicolaus Copernicus when they proposed their world-changing scientific theories.
As for Dr. Weissman, who presented some of the results published in the July 24 paper at an unrelated meeting of the Pontifical Academy of Sciences in Vatican City in April 2012, he says he was annoyed that representatives of the Catholic Church “act as if they don’t know the scientific data” and have continued to back VSELs.
But, work in the laboratory of Diane Krause, M.D., Ph.D., professor of laboratory medicine, cell biology, and of pathology and associate director, Yale Stem Cell Center, lends a modicum of support for the shadow cells if validated. Dr. Krause sent a post-doc to learn the technique for isolating the VSELs, and commented, “It was very challenging. We had to keep checking with Mariuscz on how to do things.” The team did succeed in isolating the cells from mouse BM, “coaxing” them into becoming endothelial cells, a cell type not normally expected to be derived from a BM cell precursor.
Specifically, Dr. Krause compared the level of BM derived epithelial cells after transplantation of VSELs, hematopoietic stem/progenitor cells, or other nonhematopoietic cells. VSELs, they said, clearly had the highest rate of epithelial cell formation in the lung. By transplanting VSELs from donor mice expressing H2B-GFP under a type 2 pneumocyte specific promoter, they showed that engraftment occurred by differentiation and not fusion, the investigators said. They noted that their paper is the first report of VSELs differentiating into an endodermal lineage in vivo, thereby potentially crossing germ layer lineages, and the data suggest that Oct4+ VSELs in the adult BM exhibit broad differentiation potential.
“I can only say that we manage to see these cells,” she says. “One of our postdocs went to the Ratajczak lab and learnt the technique properly.”
And the controversy will no doubt continue, as more labs try to validate the existence of VSELs and get them to differentiate. It would be good for everyone if they exist and eventually, become clinically useful. Most scientists agree that a lot more work is required to validate their existence and analyze their properties.
Meanwhile, on July 23, NeoStem announced NeoStem announced on that it will move its listing from NYSE MKT to the NASDAQ Capital Market effective with the start of trading on August 5, 2013. NeoStem will continue to trade under its existing ticker symbol “NBS”.
And according to Nature, NeoStem has expressed some caution in its recent statements about VSELs. In an email, NeoStem CEO Smith told Nature that the company “has studies in progress to determine, with robust data, whether or not VSELs have characteristics of pluripotent cells.”
This story has been corrected from an earlier version, which mistakenly referred to VSELs as VESLs. GEN regrets the error.
Do you think VSELs could be a viable alternative to embryonic stem cells?
Not sure; there needs to be more research