Cefazolin Irreversibly Inhibits Proliferation and Migration of Human Mesenchymal Stromal Cells

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 timeand dose-dependent reduction of the proliferation rate and the migratory potential. Tests of whether these effects were reversible revealed that doses ≥250 g/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

Cefazolin Irreversibly Inhibits Proliferation and Migration of Human Mesenchymal Stromal Cells

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

Comparison of hip joint cartilage degeneration assessed by histology and ex vivo optical coherence tomography

The aim of this study is to validate optical coherence tomography (OCT) in assessing human articular cartilage by means of histological analyses. Twenty resected human femoral head specimens were evaluated with OCT and histological analysis. OCT and histological evaluation was performed according to the Bear and the Mankin criteria. OCT grades and Mankin scores (total score and sub-score structure) were correlated and intra-/inter-observer agreement for repeated OCT evaluations was tested by interclass-correlation coefficient (ICC) analysis. OCT grades and Mankin scores were correlated [Spearman correlation = 0.742 (total) and 0.656 (structure), P<0.001], revealing significant differences between the histological scores in various OCT grades of cartilage degeneration (P<0.001). Intra-observer (ICC 0.930) and inter-observer (ICC 0.933) reliability was high (P<0.001). OCT appears to be reliable in the assessment of human articular cartilage. Further studies on intra-operative cartilage evaluation by OCT are necessary to substantiate its applicability in clinical routine

Biomechanical Stability and Osteogenesis in a Tibial Bone Defect Treated by Autologous Ovine Cord Blood Cells—A Pilot Study

The aim of this study was to elucidate the impact of autologous umbilical cord blood cells (USSC) on bone regeneration and biomechanical stability in an ovine tibial bone defect. Ovine USSC were harvested and characterized. After 12 months, full-size 2.0 cm mid-diaphyseal bone defects were created and stabilized by an external fixateur containing a rigidity measuring device. Defects were filled with (i) autologous USSC on hydroxyapatite (HA) scaffold (test group), (ii) HA scaffold without cells (HA group), or (iii) left empty (control group). Biomechanical measures, standardized X-rays, and systemic response controls were performed regularly. After six months, bone regeneration was evaluated histomorphometrically and labeled USSC were tracked. In all groups, the torsion distance decreased over time, and radiographies showed comparable bone regeneration. The area of newly formed bone was 82.5 ± 5.5% in the control compared to 59.2 ± 13.0% in the test and 48.6 ± 2.9% in the HA group. Labeled cells could be detected in lymph nodes, liver and pancreas without any signs of tumor formation. Although biomechanical stability was reached earliest in the test group with autologous USSC on HA scaffold, the density of newly formed bone was superior in the control group without any bovine HA

Dexamethasone modulates BMP-2 effects on mesenchymal stem cells in vitro

Dexamethasone/ascorbic acid/glycerolphosphate (DAG) and bone morphogenic protein (BMP)-2 are potent agents in cell proliferation and differentiation pathways. This study investigates the in vitro interactions between dexamethasone and BMP-2 for an osteoblastic differentiation of mesenchymal stem cells (MSCs). Bone marrow-derived human MSCs were cultured with DAG (group A), BMP-2 + DAG (group B), and DAG + BMP-2 combined with a porous collagen I/III scaffold (group C). RT-PCR, ELISA, immuncytochemical stainings and flow cytometry analysis served to evaluate the osteogenic-promoting potency of each of the above conditions in terms of cell morphology/viability, antigen presentation, and gene expression. DAG induced collagen I secretion from MSCs, which was further increased by the combination of DAG + BMP-2. In comparison, the collagen scaffold and the control samples showed no significant influence on collagen I secretion of MSCs. DAG stimulation of MSCs led also to a steady but not significant increase of BMP-2 level. A DAG and more, a DAG + BMP-2, stimulation increased the number of mesenchymal cells (CD105+/CD73+). All samples showed mRNA of ALP, osteopontin, Runx2, Twist 1 and 2, Notch-1/2, osteonectin, osteocalcin, BSP, and collagen-A1 after 28 days of in vitro culture. Culture media of all samples showed a decrease in Ca(2+) and PO(4) (2-) concentration, whereas a collagen-I-peak only occurred at day 28 in DAG- and DAG + BMP-2-stimulated bone marrow cells. In conclusion, BMP-2 enhances DAG-induced osteogenic differentiation in mesenchymal bone marrow cells. Both agents interact in various ways and can modify osteoblastic bone formation. Inc