title: Methotrexate released in vitro from bone cement inhibits human stem cell proliferation in S/G2 phase.
abstract: Methotrexate (MTX) released from bone cement showed a useful local effect in animal models of bone tumours. However, local toxic reactions such as impaired wound healing were observed in areas surrounding the MTX-loaded implant. Therefore, we hypothesised that MTX released from bone cement would have harmful effects on human mesenchymal stem cells (MSC)-one of the basic components of bone marrow and tissue reparatory processes. Moreover, elution of MTX was calculated from implants prepared either with liquid or powdered MTX. During the 28-day incubation, the cement compounded with liquid MTX showed the highest elution rate of the drug. MTX released from pellets produced a significant decrease in proliferation of MSC as a consequence of a blockade of their cell cycle in the S/G2 phase. These findings indicate impairment of stem cell function in marginal areas surrounding the MTX-loaded cement and may help to explain problems with regeneration of tissues in these locations.
authors.affiliation: Department of Orthopedic Surgery, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
authors.forename: Egon
authors.initials: E
authors.lastname: Prochazka
authors.forename: Tomas
authors.initials: T
authors.lastname: Soukup
authors.forename: Milos
authors.initials: M
authors.lastname: Hroch
authors.forename: Leos
authors.initials: L
authors.lastname: Fuksa
authors.forename: Eva
authors.initials: E
authors.lastname: Brcakova
authors.forename: Jolana
authors.initials: J
authors.lastname: Cermanova
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kolouchova
authors.forename: Karel
authors.initials: K
authors.lastname: Urban
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Mokry
authors.forename: Stanislav
authors.initials: S
authors.lastname: Micuda
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry*; D001843:Bone Cements / Q000737:chemistry*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007399:Interphase / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000473:pathology; D008727:Methotrexate / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D000964:Antimetabolites, Antineoplastic; D001843:Bone Cements; D008727:Methotrexate