Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation.
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.
Tarte
Karin
K
INSERM U917, Université Rennes 1, Rennes, France.
Gaillard
Julien
J
Lataillade
Jean-Jacques
JJ
Fouillard
Loic
L
Becker
Martine
M
Mossafa
Hossein
H
Tchirkov
Andrei
A
Rouard
Hélène
H
Henry
Catherine
C
Splingard
Marie
M
Dulong
Joelle
J
Monnier
Delphine
D
Gourmelon
Patrick
P
Gorin
Norbert-Claude
NC
Sensebé
Luc
L
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
D006684:HLA-DR Antigens