Effects of antithrombotic drugs fondaparinux and tinzaparin on in vitro proliferation and osteogenic and chondrogenic differentiation of bone-derived mesenchymal stem cells

Argiris Papathanasopoulos, Dimitrios Kouroupis, Karen Henshaw, Dennis McGonagle, Elena A. Jones, Peter V. Giannoudis

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1327-1335
Number of pages9
JournalJournal of Orthopaedic Research
Volume29
Issue number9
DOIs
StatePublished - Sep 2011
Externally publishedYes

Keywords

  • bone healing
  • chemical thromboprophylaxis
  • low molecular heparins
  • MSC

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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