Controversial reports on spontaneous transformation of MSCs

・Points to Consider in the Characterization of Cell Lines Used to Produce Biologicals 7/12/1993
http://www.fda.gov/cber/gdlns/ptccell.pdf


Spontaneous malignant transformation of human mesenchymal stem cells reflects cross-contamination: putting the research field on track - letter.
Torsvik A, R?sland GV, Svendsen A, Molven A, Immervoll H, McCormack E, L?nning PE, Primon M, Sobala E, Tonn JC, Goldbrunner R, Schichor C, Mysliwietz J, Lah TT, Motaln H, Knappskog S, Bjerkvig R.
Cancer Res. 2010 Aug 1;70(15):6393-6.

Deficiency in p53 but not retinoblastoma induces the transformation of mesenchymal stem cells in vitro and initiates leiomyosarcoma in vivo.
Rubio R, Garc?a-Castro J, Guti?rrez-Aranda I, Paramio J, Santos M, Catalina P, Leone PE, Menendez P, Rodr?guez R.
Cancer Res. 2010 May 15;70(10):4185-94.



Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation.
R?sland GV, Svendsen A, Torsvik A, Sobala E, McCormack E, Immervoll H, Mysliwietz J, Tonn JC, Goldbrunner R, L?nning PE, Bjerkvig R, Schichor C.
Cancer Res. 2009 Jul 1;69(13):5331-9.

Cancer Res. 2005 Apr 15;65(8):3035-9.
Spontaneous human adult stem cell transformation.
Rubio D, Garcia-Castro J, Mart?n MC, de la Fuente R, Cigudosa JC, Lloyd AC, Bernad A.

Department of Immunology and Oncology, Centro Nacional de Biotecnolog?a/Consejo Superior de Investigaciones Cientificas, UAM Campus de Cantoblanco, Darwin, 3 E-28049 Madrid, Spain.
Erratum in:

Cancer Res. 2005 Jun 1;65(11):4969.
Comment in:
Cancer Res. 2005 Oct 15;65(20):9601; author reply 9601.
Abstract
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.


Human bone marrow derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms.
Bernardo ME, Zaffaroni N, Novara F, Cometa AM, Avanzini MA, Moretta A, Montagna D, Maccario R, Villa R, Daidone MG, Zuffardi O, Locatelli F.
Cancer Res. 2007 Oct 1;67(19):9142-9.


Human bone marrow derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms.
Bernardo ME, Zaffaroni N, Novara F, Cometa AM, Avanzini MA, Moretta A, Montagna D, Maccario R, Villa R, Daidone MG, Zuffardi O, Locatelli F.
Cancer Res. 2007 Oct 1;67(19):9142-9.
PMID: 17909019