Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation

作者：Karin Tarte, Julien Burlaud‐Gaillard, Jean‐Jacques Lataillade, L Fouillard, Martine Becker, Hossein Mossafa, Andréï Tchirkov, Hélène Rouard, Catherine Creme Henry, Marie Splingard, Joëlle Dulong, Delphine Monnier, P. Gourmelon, Gorin Nc, Luc Sensebé, on behalf of Société Française de Greffe de Moelle et Thérapie Cellulaire · 发表于：Blood · 年份：2009 · DOI：10.1182/blood-2009-05-219907 · 被引用次数：432 · 研究领域：Mesenchymal stem cell research、Tissue Engineering and Regenerative Medicine、Cancer Cells and Metastasis

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.