title: A mesenchymal stromal cell line resistant to paclitaxel that spontaneously differentiates into osteoblast-like cells.
abstract: The mesenchymal stromal cell line SR-4987 has been established in our laboratory from the bone marrow of BDF/1 mice. Recent information on mesenchymal stem cells biology and the need to deal with well-characterized cell lines suggest to critically consider the existent data on this cell line by updating them with new investigations on growth parameters, in vitro plasticity, and drug sensitivity to anti-cancer, anti-inflammatory, and a histone deacetylase inhibitor. SR-4987 cells show a population doubling time of 24.5 ± 5.4 h, a plating efficiency of 2.87 ± 1.19%, and under stimulation maintain only in part their multipotency by differentiating towards chondro-osteogenic lineages but not into adipogenic. Surprisingly, these mesenchymal stromal cells differentiate spontaneously into osteoblast-like cells and this is significantly stimulated by valproic acid. SR-4987 cells show a dramatic resistance to paclitaxel (PTX) with a resistance index of 39.6 times (evaluated versus MOLT-4 leukemia) and of 68.2 (versus HT-29 colorectal carcinoma). SR-4987 resistance is reversed by verapamil and correlates with high expression of P-glycoprotein that is down-modulated by PTX. Taken together, our results indicated that SR-4987 line is a very interesting cell model useful to investigate both drug sensitivity resistance and physiopathological aspects related to mesenchymal cell function.
authors.affiliation: Department of Public Health–Microbiology–Virology, University of Milan, Via Pascal 36, 20133, Milan, Italy. augusto.pessina@unimi.it
authors.forename: Augusto
authors.initials: A
authors.lastname: Pessina
authors.forename: Francesca
authors.initials: F
authors.lastname: Sisto
authors.forename: Valentina
authors.initials: V
authors.lastname: Coccè
authors.forename: Loredana
authors.initials: L
authors.lastname: Cavicchini
authors.forename: Emilio
authors.initials: E
authors.lastname: Ciusani
authors.forename: Laura
authors.initials: L
authors.lastname: Gribaldo
authors.forename: Arianna
authors.initials: A
authors.lastname: Bonomi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000972:Antineoplastic Agents, Phytogenic; D014635:Valproic Acid; D017239:Paclitaxel; D001241:Aspirin; D007213:Indomethacin