Effects of antithrombotic drugs fondaparinux and tinzaparin on in vitro proliferation and osteogenic and chondrogenic differentiation of bone‐derived mesenchymal stem cells
Open Access
- 22 March 2011
- journal article
- research article
- Published by Wiley in Journal of Orthopaedic Research
- Vol. 29 (9), 1327-1335
- https://doi.org/10.1002/jor.21405
Abstract
An unexpected side effect of some classes of anticoagulants has been osteoporosis which may be, at least in part, related to deranged mesenchymal stem cell (MSC) function. The aim of the present study was to compare the effect of fondaparinux (FDP), a novel antithrombotic with a traditional widely used low molecular weight heparin, tinzaparin (TZP) on MSC proliferation and differentiation. MSCs were isolated from trabecular bone of 14 trauma patients by a collagenase‐based digestion procedure and expanded in standard conditions until passage 3. Proliferation and differentiation of MSCs to chondrocytes and osteoblasts was assessed with or without the addition of FDP and TZP using standard in vitro assays and a broad range of drug concentrations. Flow cytometry was used for MSC phenotyping. In the age studied group (17–74 years old) the MSC frequency in collagenase‐released fractions was 641/106 cells (range 110–2,158) and their growth characteristics were ∼4 days/population doubling. Cultures had a standard MSC phenotype (CD73+, CD105+, CD146+, CD106+, and CD166+). Cell proliferation was assessed by both colony‐forming unit‐fibroblast (CFU‐F) and colorimetric tetrazolium salt XTT assays. In both assays, MSC proliferation was inhibited by the addition of TZP, particularly at high concentrations. In contrast, FDP had no effect on MSC proliferation. Osteogenic differentiation and chondrogenic differentiation were not affected by the addition of either TZP or FDP. Whilst MSC proliferation, but not differentiation, is negatively affected by TZP, there was no evidence for adverse effects of FDP in this in vitro model system which argues well for its use in the orthopedic setting. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1327–1335, 2011Keywords
Funding Information
- The Wellcome Trust/EPSRC (WT 088908/Z/09/Z)
- National Institute of Health Research
This publication has 36 references indexed in Scilit:
- Large‐scale extraction and characterization of CD271+ multipotential stromal cells from trabecular bone in health and osteoarthritis: Implications for bone regeneration strategies based on uncultured or minimally cultured multipotential stromal cellsArthritis & Rheumatism, 2010
- Synovial fluid mesenchymal stem cells in health and early osteoarthritis: Detection and functional evaluation at the single‐cell levelArthritis & Rheumatism, 2008
- Replicative Senescence of Mesenchymal Stem Cells: A Continuous and Organized ProcessPLOS ONE, 2008
- Growing bone and cartilageThe Journal of Bone and Joint Surgery. British volume, 2006
- Effect of low molecular weight heparin (dalteparin) and fondaparinux (Arixtra®) on human osteoblasts in vitroBritish Journal of Surgery, 2004
- Study of Telomere Length Reveals Rapid Aging of Human Marrow Stromal Cells following In Vitro ExpansionThe International Journal of Cell Cloning, 2004
- Characterization of Multipotential Mesenchymal Progenitor Cells Derived from Human Trabecular BoneThe International Journal of Cell Cloning, 2003
- Isolation and characterization of bone marrow multipotential mesenchymal progenitor cellsArthritis & Rheumatism, 2002
- Incidence of Deep-Vein Thrombosis in Patients with Fractures of the Lower Extremity Distal to the HipJournal of Orthopaedic Trauma, 1996
- Osteoporosis and vertebral collapse following low-dose, low molecular weight heparin therapy in a young patientClinical and Laboratory Haematology, 1996