Department of Human Genetics, Liège University, Liège, Belgium.
Stem Cells Dev. 2010 Aug;19(8):1167-73. doi: 10.1089/scd.2009.0264.
Mesenchymal stem cells (MSCs) are studied as a cellular source for the treatment of various diseases. In this work, we isolated and cultivated murine bone marrow-derived MSCs. After a first observation of a solid tumor in a mouse injected with these cells, we systematically explored their chromosomal stability. We observed in all the cytogenetically analyzed cases gross chromosomal alterations every time the MSCs went through the senescence crisis while the lymphocytes from the same animals showed a normal chromosome count. This observation was confirmed in different mouse strains, with different culture protocols, and even in short-term cultures after a hematopoietic cell negative immunodepletion performed in order to accelerate the isolation procedure. Therefore, we conclude that murine MSCs display high chromosomal instability and can generate tumors, and that care must be taken before using them for the evaluation of MSC therapeutic potential.
间充质干细胞(MSCs)被研究作为一种细胞来源,用于治疗各种疾病。在这项工作中,我们分离和培养了来自鼠骨髓的间充质干细胞。在给这些细胞注射的一只老鼠体内首次观察到实体瘤后,我们系统地研究了它们的染色体稳定性。我们在所有进行细胞遗传学分析的情况下都观察到,每当 MSCs 经历衰老危机时,就会出现严重的染色体改变,而来自同一动物的淋巴细胞则显示出正常的染色体计数。这一观察结果在不同的小鼠品系、不同的培养方案中得到了证实,甚至在进行造血细胞阴性免疫耗竭以加速分离过程的短期培养中也得到了证实。因此,我们得出结论,鼠 MSCs 表现出高度的染色体不稳定性,并可能产生肿瘤,在将其用于评估 MSC 治疗潜力之前,必须谨慎对待。