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Spontaneous Human Adult Stem Cell Transformation

¹ Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas, UAM Campus de Cantoblanco; ² Oncology Department, Hospital Universitario del Niño Jesús; ³ Cytogenetics Unit, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain; and ⁴ Laboratory for Molecular Cell Biology, University College London, London, United Kingdom

Requests for reprints: Javier Garcia-Castro, Department of Immunology, Centro Nacional de Biotechnologia/Consejo Superior de Investigaciones Cientificas, UAM Campus de Cantoblanco, Darwin, 3 E-28049 Madrid, Spain. Phone: 34-915854656; Fax: 34-913720493; E-mail: igarciac.hnjs{at}salud.madrid.org.

Human adult stem cells are being evaluated widely for various therapeutic approaches. Several recent clinical trials have reported their safety, showing them to be highly resistant to transformation. The clear similarities between stem cell and cancer stem cell genetic programs are nonetheless the basis of a recent proposal that some cancer stem cells could derive from human adult stem cells. Here we show that although they can be managed safely during the standard ex vivo expansion period (6-8 weeks), human mesenchymal stem cells can undergo spontaneous transformation following long-term in vitro culture (4-5 months). This is the first report of spontaneous transformation of human adult stem cells, supporting the hypothesis of cancer stem cell origin. Our findings indicate the importance of biosafety studies of mesenchymal stem cell biology to efficiently exploit their full clinical therapeutic potential.

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