title: Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation.
abstract: 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.
authors.affiliation: INSERM U917, Université Rennes 1, Rennes, France.
authors.forename: Karin
authors.initials: K
authors.lastname: Tarte
authors.forename: Julien
authors.initials: J
authors.lastname: Gaillard
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lataillade
authors.forename: Loic
authors.initials: L
authors.lastname: Fouillard
authors.forename: Martine
authors.initials: M
authors.lastname: Becker
authors.forename: Hossein
authors.initials: H
authors.lastname: Mossafa
authors.forename: Andrei
authors.initials: A
authors.lastname: Tchirkov
authors.forename: Hélène
authors.initials: H
authors.lastname: Rouard
authors.forename: Catherine
authors.initials: C
authors.lastname: Henry
authors.forename: Marie
authors.initials: M
authors.lastname: Splingard
authors.forename: Joelle
authors.initials: J
authors.lastname: Dulong
authors.forename: Delphine
authors.initials: D
authors.lastname: Monnier
authors.forename: Patrick
authors.initials: P
authors.lastname: Gourmelon
authors.forename: Norbert-Claude
authors.initials: NC
authors.lastname: Gorin
authors.forename: Luc
authors.initials: L
authors.lastname: Sensebé
mesh_terms: D000782:Aneuploidy; D018929:Cell Culture Techniques; D002469:Cell Separation / Q000379:methods*; D002471:Cell Transformation, Neoplastic; D005786:Gene Expression Regulation; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D006684:HLA-DR Antigens