Advertisement
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

    X
  • Abraham Hirshberg,

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

    X
  • Bernd W Scheithauer,

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

    X
  • Yoram Cohen,

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

    X
  • Ron Loewenthal,

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

    X
  • Luba Trakhtenbrot,

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

    X
  • Nurit Paz,

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

    X
  • Maya Koren-Michowitz,

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

    X
  • Dalia Waldman,

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

    X
  • Leonor Leider-Trejo,

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

    X
  • Amos Toren,

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

    X
  • Shlomi Constantini,

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

    X
  • 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

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

Reader Comments (11)

Post a new comment on this article

Response to Prof. Ole Isacson

Posted by plosmedicine on 31 Mar 2009 at 00:34 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
Submitted Date: February 27, 2009
Published Date: February 27, 2009
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

We will respond to the scientific points raised by Professor Isacson:

Professor Isacson is concerned that while indeed undifferentiated neural stem cells have been proposed for stroke and trauma, the Editors’ summary states that such cells would be considered for.. “(for example, Parkinson’s disease)”. In the paper, while not mentioning Parkinson's disease (PD) specifically, we wrote that: "neural stem cells are being investigated as potential therapies for neurodegenerative diseases, stroke and trauma". We gave your publication as reference. Actually your work described in vivo therapy with naïve ES cells that when grafted in a Parkinson rat model developed into functional dopaminergic neurons. Even if most people would consider today using more differentiated cells (from ES, neural stem cells or BM derived) the risk of such experimental therapies should be borne in mind. The use of fully differentiated dopaminergic neurons in Parkinson's animal models revealed a low rate of tyrosine hydroxylase positive surviving neurons after transplantation. Therefore some groups used neuronal precursor cells in PD models. Therefore mentioning that such therapies were indeed suggested for PD was appropriate.
When dealing with innovative therapies that include isolation and processing of stem cells in culture, transforming events can potentially occur both ex vivo and in vivo.
When differentiation of stem cells is induced one can not rule out the possibility that rare cells escaped this process. Therefore one should be cautious also in cell therapies where differentiated cells are used. Such considerations were indeed raised (ref 1 in our paper): "Any ES cells that might have escaped in vitro differentiation have the potential for undifferentiated expansion potentially yielding teratomas or their derivative tumors after implantation. Thus, even though tumors have not yet been reported in primates or human ES transplants in the CNS one must me skeptical".

G. Rechavi
N. Amariglio

No competing interests declared.