Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation
Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation
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DOI：
10.1182/blood-2009-05-219907
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发表时间：
2010-02-25
期刊：
影响因子：
20.3
通讯作者：
Sensebe, Luc
中科院分区：
文献类型：
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作者：
Tarte, Karin;Gaillard, Julien;Sensebe, Luc
临床级的人间充质基质细胞（MSC）已经在体外扩增用于组织工程或免疫调节目的，而没有标准化的培养条件或释放标准。虽然人骨髓间充质干细胞对致癌转化的敏感性较差，但最近的2项研究描述了其积累染色体不稳定性的能力，并在长期培养后在免疫功能低下的小鼠中引起癌症。因此，我们研究了2个多中心临床试验中4个细胞治疗设施中用胎牛血清和成纤维细胞生长因子或血小板裂解物扩增的MSC的免疫学和遗传学特征。培养的MSC显示出人类白细胞抗原-DR的适度表达，而不改变其低免疫原性或其免疫调节能力。此外，在体外检测到一些短暂的和供体依赖性的复发性非整倍体，独立于培养过程。然而，骨髓间充质干细胞与或没有染色体改变显示渐进性生长停滞，并进入衰老，无论是在体外还是在体内没有转化的证据。（血。2010;115：1549-1553）
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. (Blood. 2010;115:1549-1553)