Study of oncogenic transformation in ex vivo expanded mesenchymal cells, from paediatric bone marrow
Study of oncogenic transformation in ex vivo expanded mesenchymal cells, from paediatric bone marrow
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DOI：
10.1111/j.1365-2184.2008.00559.x
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发表时间：
2008-12-01
影响因子：
8.5
通讯作者：
Kalmanti, M.
中科院分区：
文献类型：
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作者：
Choumerianou, D. M.;Dimitriou, H.;Kalmanti, M.
目的：间充质基质细胞(MSCs)在科学和临床领域都引起了人们的极大兴趣。为了获得足够数量的细胞用于应用，它们的体外扩增是必要的，但在这个过程中，它们的特性可能会改变，细胞可能会获得致癌特性。我们已经研究了可能与肿瘤发生有关的MSC的特性，这是在MSC临床应用之前必须评估的一个关键参数。材料和方法：对诊断为特发性血小板减少性紫癜(ITP)和自身免疫性中性粒细胞减少症的儿童骨髓间充质干细胞(MSCs)中p53、p16、Rb、H-RAS和hTERT的表达进行了研究。将相同的细胞接种在软琼脂中，以确认它们的锚定依赖性，并进行核型分析。最后，将MSCs移植到SCID小鼠皮下，并对其异位成骨和成瘤能力进行了评价。结果：ITP和自身免疫性中性粒细胞减少症患儿骨髓来源的MSCs未发生转化，细胞表达正常水平的p53、p16、Rb和H-RAS。未检测到hTERT的表达，染色体内容保持稳定，证实了它们的锚定依赖性。在活体模型中，当MSCs被移植到SCID小鼠的皮下时，没有观察到肿瘤形成。结论：这些发现表明，来自儿童骨髓的MSCs不具有致癌特性，因此是再生医学应用的有效候选者。
Objectives: Mesenchymal stromal cells (MSCs) have attracted considerable interest in both the scientific and clinical fields. In order to obtain a sufficient cell number for application, their in vitro expansion is necessary, but during this process their characteristics may be altered and cells may acquire oncogenic properties. We have investigated properties of MSC that may be related to oncogenesis, a critical parameter that has to be evaluated prior to MSC clinical use. Materials and methods: We studied the expression of p53, p16, RB, H-RAS and human telomerase reverse transcriptase (hTERT) in MSCs from bone marrow of children diagnosed with idiopathic thrombocytopenic purpura (ITP) and autoimmune neutropenia. The same cells were seeded in soft agar to confirm their anchorage dependence and were karyotypically analysed. Finally, MSCs were subcutaneously transplanted into SCID mice and their ectopic osteogenic as well as tumorigenic potential was evaluated. Results: We have shown that MSCs derived from bone marrow of children with ITP and autoimmune neutropenia do not undergo transformation, the cells expressed normal levels of p53, p16, RB and H-RAS. Expression of hTERT was undetectable, chromosome content remained stable, and their anchorage dependence was confirmed. In an in vivo model, when MSCs were subcutaneously transplanted into SCID mice, no tumorigenesis was observed. Conclusions: These findings suggest that MSCs from bone marrow of children do not have oncogenic properties and, therefore, represent validate candidates for applications in regenerative medicine.