期刊
CANCER RESEARCH
卷 69, 期 13, 页码 5331-5339出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-08-4630
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资金
- Norwegian Cancer Society
- Norwegian Research Council
- Innovest Program on Quality Research
- Helse-Vest
- Haukeland University Hospital
- Bergen Translational Research Program
- Centre de Recherche de Public de la Sante (CRP-Sante) through a grant from the Research Ministry in Luxembourg
- European Commission [504743]
- Binational SYSTHER-INREMOS Virtual Institute
- German and Slovenian Federal Ministries of Education and Research
- German Society of Neurosurgery
Human mesenchymal stem cells (hMSC) aid in tissue maintenance and repair by differentiating into specialized cell types. Due to this ability, hMSC are currently being evaluated for cell-based therapies of tissue injury and degenerative diseases. However, extensive expansion ex vivo is a prerequisite to obtain the cell numbers required for human cell-based therapy protocols. Recent studies indicate that hMSC may contribute to cancer development and progression either by acting as cancer-initiating cells or through interactions with stromal elements. If spontaneous transformation ex vivo occurs, this may jeopardize the use of hMSC as therapeutic tools. Whereas murine MSC readily undergo spontaneous transformation, there are conflicting reports about spontaneous transformation of hMSC. We have addressed this controversy in a two-center study by growing bone marrow-derived hMSC in long-term cultures (5-106 weeks). We report for the first time spontaneous malignant transformation to occur in 45.8% (11 of 24) of these cultures. In comparison with hMSC, the transformed mesenchymal cells (TMC) showed a significantly increased proliferation rate and altered morphology and phenotype. In contrast to hMSC, TMC grew well in soft agar assays and were unable to undergo complete differentiation. Importantly, TMC were highly tumorigenic, causing multiple fast-growing lung deposits when injected into immunodeficient mice. We conclude that spontaneous malignant transformation may represent a biohazard in long-term ex vivo expansion of hMSC. On the other hand, this spontaneous transformation process may represent a unique model for studying molecular pathways initiating malignant transformation of hMSC. [Cancer Res 2009;69(13):5331-9]
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