Spontaneous human adult stem cell transformation.

By Daniel Rubio, J. García-Castro, M. C. Martín, R. de la Fuente, J. Cigudosa, A. Lloyd, A. Bernad. Cancer Research, 2005

1,092 citations recorded by the source corpus.

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.

Subfields: Biotechnology, Genetics, Surgery

View Paper: https://www.semanticscholar.org/paper/9012a61ec571f87acf3b8afe828dea6c292a9634

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Citations in the corpus

• Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation. (2009, background): “00003), in agreement with previous reports on malignant transformation (11, 22).”
• Tumor microenvironment: The role of the tumor stroma in cancer (2007, background): “MSChave been reported to be inherently mutagenic, undergoing genetic alterations as a result of forced divisions [Serakinci et al., 2004; Rubio et al., 2005].”
• Mesenchymal Stem Cells Are Recruited into Wounded Skin and Contribute to Wound Repair by Transdifferentiation into Multiple Skin Cell Type1 (2008, neutral): “1 mM indomethacine (Sigma-Aldrich) (21).”
• Tissue engineering approaches to develop cultured meat from cells: A mini review (2017, background): “Adipose tissue-derived adult stem cells have been observed to immortalize at high frequency and undergo rapid transformation in long-term culturing (Rubio et al., 2005).”
• Mesenchymal Stem Cells Derived from Dental Tissues vs. Those from Other Sources: Their Biology and Role in Regenerative Medicine (2009, background): “Careful monitoring and observation of this possibility are of paramount important, since evidence has shown that adipose-derived MSCs lost genetic stability over time and are prone to tumor formation (Rubio et al., 2005).”
• Cancer Stem Cells (CSCs) in Drug Resistance and their Therapeutic Implications in Cancer Treatment (2018, background): “Moreover, long-term culture can also induce telomerase-transduced adult human mesenchymal stem cells (hMSCs) to undergo spontaneous transformation, showing that these cells are also the origin of CSCs [43, 44].”
• Sarcoma Derived from Cultured Mesenchymal Stem Cells (2007, background): “In addition, conditions of prolonged culture (4–5 months, as reported for human MSCs) [ 43 ] favor cells with rapid proliferation potential and minimal contact inhibition.”
• Human bone marrow derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms. (2007, background): “In contrast to what has been recently described by Rubio et al. ( 20 ) for human, adipose tissue–derived MSCs, none of our MSC samples bypassed the senescence period by developing a crisis phase characterized by a cell cycle rate accelerated compared with presenescence MSCs.”
• Prospectus of cultured meat—advancing meat alternatives (2011, background): “It has been observed that adipose tissue-derived adult stem cells immortalize at high frequency and undergo spontaneous transformation in long-term (4–5 months) culturing (Rubio et al. 2005), while evidence of adult stem cells remaining untransformed have also been reported (Bernardo et al.”
• Aging of mesenchymal stem cell in vitro (2006, neutral): “Rubiro et al.[22] demonstrated that adipocyte tissue derived hMSC under long term culture conditions, upon entering old age, spontaneously transform into small, clustered aggregations disLong term growth curves; each obtained from an individual d or Figu 2 Long term growth curves; each obtained from”