Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
International Orthopaedics
Published in: International Orthopaedics 1/2010

01-01-2010 | Original Paper

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

Authors: Egon Prochazka, Tomas Soukup, Milos Hroch, Leos Fuksa, Eva Brcakova, Jolana Cermanova, Gabriela Kolouchova, Karel Urban, Jaroslav Mokry, Stanislav Micuda

Published in: International Orthopaedics | Issue 1/2010

Login to get access

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.
Literature
1.
Hernigou P, Thiery JP, Benoit J, Voisin MC, Leroux P, Hagege G, Delepine G, Goutallier D (1989) Methotrexate diffusion from acrylic cement. Local chemotherapy for bone tumours. J Bone Joint Surg Br 71:804–811PubMed
2.
Maccauro G, Cittadini A, Casarci M, Muratori F, De AD, Piconi C, Rosa MA, Spadoni A, Braden M, Sgambato A (2007) Methotrexate-added acrylic cement: biological and physical properties. J Mater Sci Mater Med 18:839–844CrossRefPubMed
3.
Wang HM, Galasko CSB, Crank S, Oliver G, Ward CA (1995) Methotrexate loaded acrylic cement in the management of skeletal metastases-biomechanical, biological, and systemic effect. Clin Orthop Relat Res 312:173–186PubMed
4.
Wang HM, Crank S, Oliver G, Galasko CSB (1996) The effect of methotrexate-loaded bone cement on local destruction by the VX(2) tumour. J Bone Joint Surg Br 78B:14–17
5.
Kim HS, Park YB, Oh JH, Yoo KH, Lee SH (2001) The cytotoxic effect of methotrexate loaded bone cement on osteosarcoma cell lines. Int Orthop 25:343–348CrossRefPubMed
6.
Kirchen ME, Menendez LR, Lee JH, Marshall GJ (1996) Methotrexate eluted from bone cement: effect on giant cell tumor of bone in vitro. Clin Orthop Relat Res 328:294–303CrossRefPubMed
7.
Decker S, Winkelmann W, Nies B, van VF (1999) Cytotoxic effect of methotrexate and its solvent on osteosarcoma cells in vitro. J Bone Joint Surg Br 81:545–551CrossRefPubMed
8.
Jiang YH, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du JB, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49CrossRefPubMed
9.
Borovecki F, Pecina-Slaus N, Vukicevic S (2007) Biological mechanisms of bone and cartilage remodelling–genomic perspective. Int Orthop 31:799–805CrossRefPubMed
10.
Hoffmann A, Gross G (2007) Tendon and ligament engineering in the adult organism: mesenchymal stem cells and gene-therapeutic approaches. Int Orthop 31:791–797CrossRefPubMed
11.
Tatatarenko-Kozmina TY, Denisov-Nikol’skii YI, Volozhin AI, Doktorov AA, Mal’ginov NN, Krasnov AP (2007) Effect of hydroxyapatite as a component of biostable composites on population and proliferation of mesenchymal stem cells. Bull Exp Biol Med 143:519–523CrossRefPubMed
12.
Chang YH, Goldberg VM, Caplan AI (2006) Toxic effects of gentamicin on marrow-derived human mesenchymal stem cells. Clin Orthop Relat Res 452:242–249CrossRefPubMed
13.
Viateau V, Guillemin G, Bousson V, Oudina K, Hannouche D, Sedel L, Logeart-Avramoglou D, Petite H (2007) Long-bone critical-size defects treated with tissue-engineered grafts: A study on sheep. J Orthop Res 25:741–749CrossRefPubMed
14.
Fuksa L, Brcakova E, Cermanova J, Hroch M, Chladek J, Kolouchova G, Malakova J, Martinkova J, Staud F, Micuda S (2008) Amiodarone modulates pharmacokinetics of low-dose methotrexate in rats. Biopharm Drug Dispos 29:289–299CrossRefPubMed
15.
Reyes M, Lund T, Lenvik T, Aguiar D, Koodie L, Verfaillie CM (2001) Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood 98:2615–2625CrossRefPubMed
16.
Downes S (1991) Methods for improving drug release from poly(methyl)methacrylate bone cement. Clin Mater 7:227–231CrossRefPubMed
17.
Huang RF, Ho YH, Lin HL, Wei JS, Liu TZ (1999) Folate deficiency induces a cell cycle-specific apoptosis in HepG2 cells. J Nutr 129:25–31PubMed
18.
Taylor IW, Tattersall MH (1981) Methotrexate cytotoxicity in cultured human leukemic cells studied by flow cytometry. Cancer Res 41:1549–1558PubMed
Metadata
Title
Methotrexate released in vitro from bone cement inhibits human stem cell proliferation in S/G2 phase
Authors
Egon Prochazka
Tomas Soukup
Milos Hroch
Leos Fuksa
Eva Brcakova
Jolana Cermanova
Gabriela Kolouchova
Karel Urban
Jaroslav Mokry
Stanislav Micuda
Publication date
01-01-2010
Publisher
Springer-Verlag
Published in
International Orthopaedics / Issue 1/2010
Print ISSN: 0341-2695
Electronic ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-008-0717-6

Other articles of this Issue 1/2010

International Orthopaedics 1/2010 Go to the issue

Original Paper

Depression and somatisation influence the outcome of total hip replacement

Editorial

Special years for International Orthopaedics

Original Paper

Risk factors for accelerated polyethylene wear and osteolysis in ABG I total hip arthroplasty

Original Paper

A symptom-based classification for shoulders with massive rotator cuff defects

Review

Efficacy of minimally invasive techniques for enhancement of fracture healing: evidence today

Original Paper

Are “knife and fork” good enough for day case surgery of resistant tennis elbow?