Development and functional characterization of human bone marrow mesenchymal cells immortalized by enforced expression of telomerase.
To create immortal mesenchymal cell lines, we transduced primary human bone marrow mesenchymal cells with telomerase reverse transcriptase (TERT). TERT+ mesenchymal cells continued to grow for > 2 years; parallel TERT- cultures underwent senescence after 15 weeks. TERT+ mesenchymal cells did not form foci in soft agar, had a normal karyotype and could differentiate into osteoblasts and chondrocytes. Their capacity to support leukaemic lymphoblasts and normal CD34+ haematopoietic cells was equal to or greater than that of primary cells; 42 TERT+ mesenchymal cell clones varied in their supporting capacity. Immortalized mesenchymal cells offer a promising tool for identifying molecules that regulate human haematopoiesis.
Mihara
Keichiro
K
Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.
Imai
Chihaya
C
Coustan-Smith
Elaine
E
Dome
Jeffrey S
JS
Dominici
Massimo
M
Vanin
Elio
E
Campana
Dario
D
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000201:enzymology; D002454:Cell Differentiation; D002455:Cell Division; D002461:Cell Line, Transformed; D016922:Cellular Senescence; D004268:DNA-Binding Proteins; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D009368:Neoplasm Transplantation; D019098:Telomerase / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C509186:TERT protein, human; D019098:Telomerase; C509187:Tert protein, mouse