title: Cefazolin Irreversibly Inhibits Proliferation and Migration of Human Mesenchymal Stromal Cells.
abstract: Drugs may have a significant effect on postoperative bone healing by reducing the function of human mesenchymal stromal cells (hMSC) or mature osteoblasts. Although cefazolin is one of the most commonly used antibiotic drugs in arthroplasty to prevent infection worldwide, there is a lack of information regarding how cefazolin affects hMSC and therefore may have an effect on early bone healing. We studied the proliferation and migration capacity of primary hMSC during cefazolin treatment at various doses for up to 3 days, as well as the reversibility of the effects during the subsequent 3 days of culture without the drug. We found a time- and dose-dependent reduction of the proliferation rate and the migratory potential. Tests of whether these effects were reversible revealed that doses ≥ 250 μg/mL or treatments longer than 24 h irreversibly affected the cells. We are the first to show that application of cefazolin irreversibly inhibits the potential of hMSC for migration to the trauma site and local proliferation. Cefazolin should be administered only at the required dosage and time to prevent periprosthetic infection. If long-term administration is required and delayed bone healing is present, cefazolin application must be considered as a cause of delayed bone healing.
authors.affiliation: Department of Orthopaedic Surgery, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
authors.forename: Hakan
authors.initials: H
authors.lastname: Pilge
authors.affiliation: Department of Orthopaedic Surgery, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Fröbel
authors.affiliation: Department of Orthopaedic Surgery, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Lensing-Höhn
authors.affiliation: Department of Orthopaedic Surgery, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Zilkens
authors.affiliation: Department of Orthopaedic Surgery, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Krauspe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002437:Cefazolin / Q000633:toxicity*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D017102:Fracture Healing / Q000187:drug effects; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D008875:Middle Aged; D008954:Models, Biological; D055815:Young Adult
chemical_list: D002437:Cefazolin