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Research Article

Donor-Derived Brain Tumor Following Neural Stem Cell Transplantation in an Ataxia Telangiectasia Patient

  • Ninette Amariglio,

    Affiliations: Cancer Research Center, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel, Institute of Hematology, Sheba Medical Center, Tel Hashomer, Israel

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  • Abraham Hirshberg,

    Affiliation: Department of Oral Pathology, School of Dental Medicine, Tel Aviv University, Tel-Aviv, Israel

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  • Bernd W Scheithauer,

    Affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America

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  • Yoram Cohen,

    Affiliation: Cancer Research Center, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel

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  • Ron Loewenthal,

    Affiliation: Tissue Typing Laboratory, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel

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  • Luba Trakhtenbrot,

    Affiliation: Institute of Hematology, Sheba Medical Center, Tel Hashomer, Israel

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  • Nurit Paz,

    Affiliation: Cancer Research Center, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel

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  • Maya Koren-Michowitz,

    Affiliation: Institute of Hematology, Sheba Medical Center, Tel Hashomer, Israel

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  • Dalia Waldman,

    Affiliation: Department of Pediatric Hemato-Oncology, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel

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  • Leonor Leider-Trejo,

    Affiliation: Institute of Pathology, Tel-Aviv Medical Center, Tel-Aviv, Israel

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  • Amos Toren,

    Affiliation: Department of Pediatric Hemato-Oncology, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel

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  • Shlomi Constantini,

    Affiliation: Pediatric Neurosurgery, Dana Children's Hospital, Tel-Aviv Medical Center, and Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel

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  • Gideon Rechavi mail

    To whom correspondence should be addressed. E-mail: gidi.rechavi@sheba.health.gov.il

    Affiliations: Cancer Research Center, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel, Department of Pediatric Hemato-Oncology, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel

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  • Published: February 17, 2009
  • DOI: 10.1371/journal.pmed.1000029

Reader Comments (11)

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Misleading title

Posted by doering on 19 Nov 2009 at 18:36 GMT

I have just become aware of this paper. First, I am perplexed with the title of the paper. The title is inappropriate/inaccurate for the content presented. There is absolutely no scientific evidence in this paper to indicate that
1. Neural stem cells were being isolated and expanded or
2. The tumor originated from neural stem cells.

It is clear from the data provided that the tumor did originate from the donor cells. There is no data to support the author’s claim that the cells originated from neural stem cells!
The methods in the supplementary data (Text S1) are poorly written and unsatisfactory for a research journal. There is no data showing the potential of the transplanted cells to form neurons, astrocytes and oligodendrocytes. In addition, I did not find any mention of a single control to demonstrate the specificity of the antibodies used in the immunohistochemical analysis.

Once again, there are several errors and omissions in this paper to conclusively state that the tumor originated from neural stem cells.

No competing interests declared.

RE: Misleading title

plosmedicine replied to doering on 07 Dec 2009 at 19:15 GMT

Author: Gideon Rechavi
Position: Professor
Institution: Cancer Research Center, Sheba Medical Center and Sackler School of Medicine
E-mail: gidi.rechavi@sheba.health.gov.il
Additional Authors: Ninette Amariglio

Dr Doering questions the accuracy of the title of the paper claiming that there is no proof that the tumor originated from stem cells. The team in Moscow used a protocol that is similar to experimental protocols used at the time for neural stem cell expansion. The protocol attached in the supplement (Text S1) is what was given to the family by the Russian team and we can not take responsibility for its poor quality. On the contrary, as we made it very clear in our paper, we strongly opposed the decision of the family to go through this procedure in Moscow.
The protocol used, similar to more modern protocols for neural stem cell expansion, is based on the use of mitogenic growth factors. We would like to draw attention to a recent paper (PLoS One. 2009 Oct 29; 4(10):e7630.) documenting the occurrence of chromosome 7 and 19 trisomy in fetal-derived human neural progenitor cells (hNPCs) expanded by more up to date protocols. This is another indication that a cautious approach should be taken if neural stem cells are to be advanced to the clinic. The tumor that developed in our patient was composed of donor derived neurons, astrocytes and ependymal cells. There is documented continuous growth (8 fold over three years) of the mass that was not resected so far. We did not claim that the cells given to the patient were a pure, well characterized stem cell population. However the continuous growth of the mass and the demonstration of both neuronal and glial cells from donor origin indicate that, even if hNPCs constituted only a minor fraction of the transplant, this fraction was sufficient to give rise to a tumor. We feel therefore that the title is not misleading.
Actually, if no stem cells were present in the transplant, then the fact that mature neural cells can continuously grow for years is even more sensational.

G. Rechavi
N. Amariglio
Sheba Cancer Research Center

No competing interests declared.