Thursday, March 22, 2007

Stem Cells at BigU
Curiouser and curiouser...

The stem cell brouhaha (or worse) continues at BigU. An earlier post serves as an introduction. The sleuths at New Scientist have done further digging and uncovered:

Fresh questions surround some of the highest-profile research on adult stem cells. For the second time, New Scientist has discovered apparently duplicated data being used to describe results from different experiments in work published by a group of scientists at the University of Minnesota, Minneapolis.

Now New Scientist has examined a US patent (number 7015037) granted in 2006 that covers the isolation and use of MAPCs. The patent is exclusively licensed to a company called Athersys of Cleveland, Ohio, which hopes to launch clinical trials of the cells to treat conditions including heart attacks and stroke.

Within the patent are three images that appear to be duplicated from another paper from Verfaillie's group, published in 2001 in the journal Blood (vol 98, pp 2615-2625). These images relate to experiments in which MAPCs were grown in culture dishes and made to differentiate into other cell types, such as those found in bone, cartilage, fat and the linings of blood vessels. The images document the presence of proteins specific to each type of cell being produced.

The problem is that in each case the duplicated image is used in the patent to describe the production of a different protein from that described in the Blood paper.

In the most striking example, one of the duplicated images also seems to be used twice within the Blood paper itself, to represent the results from two different experiments. In the Blood paper, this image, which shows a series of three bands on a gel, is first used to represent a control for an experiment in which a culture of stem cells is made to differentiate into cells found in bone. What seems to be the same image is used later on the same page, though this time it is flipped over horizontally, producing a mirror image, and contains some small modifications (see top two images, right). Here, it is labelled as showing the production of collagen in a culture of stem cells made to turn into cells found in cartilage.

“One of the duplicated images seems to be used twice in the Blood paper to represent results from different experiments”

In the patent, this flipped and modified image appears again, this time supposedly representing a bone-specific protein found in a culture of stem cells made to differentiate into bone cells (see bottom image, right).

The research described in the Blood paper formed part of the PhD work of its first author, Morayma Reyes, and the duplicated images in the paper, including the flipped and modified version, also appear in her thesis. Now at the University of Washington in Seattle, Reyes is named on the patent as one of the inventors, along with Verfaillie, who was her supervisor, and Leo Furcht, who heads the department of laboratory medicine and pathology at the University of Minnesota. Currently president of the Federation of American Societies for Experimental Biology, Furcht founded a company called MCL that was assigned the patent jointly with the University of Minnesota.

Stem cell biologists contacted by New Scientist are sure that the three images referred to above are duplicates. "They're quite clearly the same," says Jeanne Loring of the Burnham Institute for Medical Research in La Jolla, California. "It appears that a piece of data has been used multiple times to represent different things," agrees Arnold Kriegstein, who heads the programme in developmental and stem cell biology at the University of California, San Francisco.

Although the Blood paper is less well known than the publication that followed in Nature, it is significant in terms of the planned clinical trials because it describes cells isolated from the bone marrow of human volunteers rather than experimental mice.

“The Blood paper is significant because it describes cells isolated from the bone marrow of human volunteers”

Verfaillie, who is now at the Catholic University of Leuven (KUL) in Belgium, and Reyes were unavailable to respond to questions from New Scientist asking for an explanation of the apparent duplications. Athersys said it would review the points we raised, while the University of Minnesota said it had no comment.

After being contacted by New Scientist, Blood is now conducting its own inquiry. "We're going to do a serious investigation into this," says the journal's editor-in-chief, Sanford Shattil, a haematologist at the University of California, San Diego.

No doubt we will be hearing more about this situation in the future.



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