Fraud fells Alzheimer’s “made to order” neurons paper in Cell

In 2011, a group of researchers at Columbia University reported in Cell that they had been able to convert skin cells from patients with Alzheimer’s disease into functioning neurons — a finding that raised the exciting prospect of “made to order” brain cells for patients with the degenerative disease. As one researcher not involved with the study, led by Asa Abeliovich, put it:

“[This is] simply a remarkable and complete piece of work which will now set a standard for stem cell work in neurological disease. The standard of the characterization of the neuronal cultures is very high,” John Hardy at University College London, U.K., wrote to [Alzforum]. He was not involved in the work but is taking a similar approach in his own lab.

According to the abstract of “Directed Conversion of Alzheimer’s Disease Patient Skin Fibroblasts into Functional Neurons:”

Directed conversion of mature human cells, as from fibroblasts to neurons, is of potential clinical utility for neurological disease modeling as well as cell therapeutics. Here, we describe the efficient generation of human-induced neuronal (hiN) cells from adult skin fibroblasts of unaffected individuals and Alzheimer’s patients, using virally transduced transcription regulators and extrinsic support factors. hiN cells from unaffected individuals display morphological, electrophysiological, and gene expression profiles that typify glutamatergic forebrain neurons and are competent to integrate functionally into the rodent CNS. hiN cells from familial Alzheimer disease (FAD) patients with presenilin-1 or -2 mutations exhibit altered processing and localization of amyloid precursor protein (APP) and increased production of Aβ, relative to the source patient fibroblasts or hiN cells from unaffected individuals. Together, our findings demonstrate directed conversion of human fibroblasts to a neuronal phenotype and reveal cell type-selective pathology in hiN cells derived from FAD patients.

But the paper — which has been cited 110 times, according to Thomson Scientific’s Web of Knowledge — has now been retracted. Per the notice:

In this paper, we described the directed conversion of skin fibroblasts from unaffected individuals or familial Alzheimer’s disease patients into human induced neuronal cells. We also presented molecular analyses of Alzheimer’s-associated markers in these cells. Dr. Ryousuke Fujita, who was specifically and only responsible for the molecular analyses of Alzheimer’s-associated pathology, has acknowledged inappropriately manipulating image panels and data points, as well as misrepresenting the number of repeats performed, in the experiments presented in Figures 6 and 7 of the paper (and corresponding Figures S5 and S6). We are in the process of repeating these analyses. Given these issues, we believe that the most appropriate course of action is to retract the paper. We deeply regret this circumstance and apologize to the community.

So far this is the only retraction we’ve seen involving Fujita. But his list of publications isn’t small.

The link to an August 2011 press release from Columbia about the study is no longer working. But you can read it here:

Columbia University Medical Center researchers have for the first time directly converted human skin cells into functional forebrain neurons, without the need for stem cells of any kind. The findings offer a new and potentially more direct way to produce replacement cell therapies for Alzheimer’s and other neurodegenerative diseases. Such cells may prove especially useful for testing new therapeutic leads. The study was published in the August 4 online issue of the journal Cell.

In another first, the researchers used this method — called direct reprogramming — to generate neurons from skin cells of patients with familial (early-onset) Alzheimer’s disease. The induced neurons were found to differ significantly from those made from healthy individuals, providing new insights into the development of the disease, reports study leader Asa Abeliovich, MD, PhD, associate professor of pathology & cell biology and neurology in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at Columbia University Medical Center (CUMC).

Update 1:30 pm, April 11: We asked a Columbia spokesman about the takedown, and this is what he said:

[W]e treat questions raised about the legitimacy of research findings with the utmost seriousness, and we deeply regret that the conduct of one of our former employees in this instance caused the retraction of this paper. The press release was not taken down in response to the retraction, but in anticipation of the retraction, before it was published.

That’s all fine, but we guess transparency would have been better served had the university given the reason it yanked the press release rather than simply tried to forget it ever existed.