Methotrexate released in vitro from bone cement inhibits human stem cell proliferation in S/G2 phase.

Department of Orthopedic Surgery, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
International Orthopaedics (Impact Factor: 2.32). 03/2009; 34(1):137-42. DOI: 10.1007/s00264-008-0717-6
Source: PubMed

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.

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