INSERM U917, Université Rennes 1, Rennes, France.
Blood. 2010 Feb 25;115(8):1549-53. doi: 10.1182/blood-2009-05-219907. Epub 2009 Dec 23.
Clinical-grade human mesenchymal stromal cells (MSCs) have been expanded in vitro for tissue engineering or immunoregulatory purposes without standardized culture conditions or release criteria. Although human MSCs show poor susceptibility for oncogenic transformation, 2 recent studies described their capacity to accumulate chromosomal instability and to give rise to carcinoma in immunocompromised mice after long-term culture. We thus investigated the immunologic and genetic features of MSCs expanded with fetal calf serum and fibroblast growth factor or with platelet lysate in 4 cell-therapy facilities during 2 multicenter clinical trials. Cultured MSCs showed a moderate expression of human leukocyte antigen-DR without alteration of their low immunogenicity or their immunomodulatory capacity. Moreover, some transient and donor-dependent recurring aneuploidy was detected in vitro, independently of the culture process. However, MSCs with or without chromosomal alterations showed progressive growth arrest and entered senescence without evidence of transformation either in vitro or in vivo.
临床级别的人骨髓间充质基质细胞（MSCs）已在体外进行扩增，用于组织工程或免疫调节目的，但没有标准化的培养条件或释放标准。尽管人 MSCs 显示出对致癌转化的低易感性，但最近的 2 项研究描述了它们在长期培养后在免疫功能低下的小鼠中积累染色体不稳定性并产生癌的能力。因此，我们在 2 项多中心临床试验期间，在 4 个细胞治疗设施中使用胎牛血清和成纤维细胞生长因子或血小板裂解液扩增 MSCs ，并研究了其免疫和遗传特征。培养的 MSCs 表现出中等水平的人白细胞抗原-DR 表达，而其低免疫原性或免疫调节能力没有改变。此外，在体外检测到一些短暂的、供体依赖性的非整倍体，这与培养过程无关。然而，具有或不具有染色体改变的 MSCs 在体外或体内均表现出进行性生长停滞并进入衰老，没有转化的证据。
