Long-term Cultures of Bone Marrow-Derived Human Mesenchymal Stem Cells Frequently Undergo Spontaneous Malignant Transformation (This article contains errors due to a cross contamination of the cell lines we used. To correct this issue we published a letter in Cancer Res. 2010 Aug 1,70(15),6393-6)
Long-term Cultures of Bone Marrow-Derived Human Mesenchymal Stem Cells Frequently Undergo Spontaneous Malignant Transformation (This article contains errors due to a cross contamination of the cell lines we used. To correct this issue we published a letter in Cancer Res. 2010 Aug 1,70(15),6393-6)
复制标题
DOI：
10.1158/0008-5472.can-08-4630
复制
发表时间：
2009-07-01
期刊：
影响因子：
11.2
通讯作者：
Schichor, Christian
中科院分区：
文献类型：
--
作者：
Rosland, Gro Vatne;Svendsen, Agnete;Schichor, Christian
人类间充质干细胞（hMSC）通过分化成专门的细胞类型来帮助组织维护和修复。由于这种能力，目前正在评估hMSC用于组织损伤和退行性疾病的基于细胞的疗法。然而，离体广泛扩增是获得基于人细胞的治疗方案所需的细胞数量的先决条件。最近的研究表明，hMSC可能有助于癌症的发展和进展，无论是作为癌症起始细胞或通过与基质元素的相互作用。如果发生离体自发转化，这可能危及hMSC作为治疗工具的用途。尽管鼠MSC容易进行自发转化，但关于hMSC的自发转化存在相互矛盾的报道。我们在一项双中心研究中通过长期培养（5-106周）骨髓来源的hMSC来解决这一争议。我们首次报告自发恶性转化发生在45.8%（11/24）的这些文化。与hMSC相比，转化的间充质细胞（TMC）表现出显着增加的增殖率和改变的形态和表型。与hMSC相反，TMC在软琼脂测定中生长良好，并且不能进行完全分化。重要的是，TMC具有高度致瘤性，当注射到免疫缺陷小鼠中时，会导致多个快速生长的肺沉积物。我们的结论是，自发性恶性转化可能是一种生物危害，在长期的体外扩增的hMSC。另一方面，这种自发转化过程可能代表了一种独特的模型，用于研究引发hMSC恶性转化的分子途径。[Cancer Res 2009;69（13）：5331-9]
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]