Doubt cast over tiny stem cells

Mariusz Ratajczak first reported finding very small embryonic-like stem cells in 2006.

University of Louisville Health Sciences Center

Does a rare and minuscule cell type with the potential to repair almost any tissue in the body really exist?

Proponents of very small embryonic-like cells (VSELs) extracted from bone marrow say that the cells have the potential to transform regenerative medicine. A trial has begun in Poland, and cell-therapy company Neostem in New York is planning another in Michigan.

But in a major blow to the field, a paper published on 24 July in Stem Cell Reports suggests that the diminutive stem cells are not real1. Led by Irving Weissman, a prominent stem-cell researcher at Stanford University in California, the study is the fourth to refute the cells existence and the most thorough yet.

Weissmans evidence is a clincher it is the end of the road for VSELs, believes Rdiger Alt, head of research at Vita 34, a private bank for umbilical cord blood in Leipzig, Germany, who last year published the first failure to replicate claims for the cells2.

Robin Smith, chief executive at Neostem, disagrees. She compares the attacks on VSELs to those suffered by Charles Darwin and Nicolaus Copernicus when they proposed their world-changing scientific theories.

The battle over VSELs has been raging for more than two years, and has covered ground from the United States to Vatican City and Poland. The cells were first described3 in mouse bone marrow in 2006, by a team led by Mariusz Ratajczak at the University of Louisville in Kentucky. His group and a few others have since generated a literature that characterizes VSELs as rare components of bone marrow and other tissues, less than 6micrometres in diameter and able to turn into a diverse range of cell types, including blood, bone, muscle and nerve.

Ratajczak was given a joint position at the Pomeranian Medical University in Szczecin, Poland, in 2006. From there, he obtained 10.6million (US$14 million) from European Union sources for a VSEL research network involving five institutions. The network last year registered the first human trial of a VSEL preparation, which aims to treat 60 people who have severe angina. Around one-quarter of the participants have already been injected with the preparation.

But the network became rattled after one collaborator, Jzef Dulak at the Jagiellonian University in Krakow, failed to find traces of VSELs in his experiments. When he published his findings in May4, Ratajczak tried to force him out of the consortium. Dulak, like Weissman, found no molecular signatures associated with pluripotency in any mouse bone-marrow cells smaller than 7micrometres across. Weissmans more extensive analysis now also reports that in his experiments, the small cells did not aggregate into spheres in vitro, as pluripotent cells do; nor could they differentiate into blood cells, the adult tissues that such cells are most likely to become.

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Doubt cast over tiny stem cells