Affiliations: Department of Trauma Surgery, University Hospital of Regensburg, 93053 Regensburg, Germany | Department of Surgery, Ludwig Maximilians University, Klinikum Großhadern, 81377 Munich, Germany
Note: [] Address for correspondence: Peter Angele, MD, Department of Trauma Surgery, University Hospital of Regensburg, Franz Josef Strauss Allee 11, 93053 Regensburg, Germany. Tel.: +49 941 944 6805; Fax: +499 41 944 6806; E-mail: [email protected].
Abstract: This study examined the effects of low intensity pulsed ultrasound (LIPUS) on human bone marrow-derived mesenchymal stem cells undergoing chondrogenic differentiation. Aggregates of mesenchymal stem cells and mesenchymal stem cells seeded in three dimensional matrices were cultured in a defined chondrogenic medium and subjected to LIPUS for the first 7 days of culture. At 1, 7, 14 and 21 days, samples were harvested for histology, immunohistochemistry, RT-PCR, and quantitative DNA and matrix macromolecule analysis. Cell aggregates with daily treatment for 20 minutes showed no significant differences for proteoglycan and collagen content during chondrogenic differentiation. However ultrasound application for 40 minutes daily resulted in a statistically significant increase of the proteoglycan and collagen content after 21 days in culture. Aggregates treated for 20 minutes daily showed decreased expression of chondrogenic genes at all time points. In contrast, 40 minutes of daily treatment of aggregates resulted in a significant increase of chondrogenic marker genes after an initial decrease at day 7 with time in culture. Ultrasound treated cell-scaffold constructs showed a significant increase of chondrogenic marker gene expression and extracellular matrix deposition. This study indicates that LIPUS can be used to enhance the chondrogenesis of mesenchymal stem cells in cell aggregates and cell-scaffold constructs. We have found a dependency on the specific treatment parameters. We hypothesize that LIPUS can be used for an improved in vitro preparation of optimized tissue engineering implants for cartilage repair. Furthermore this non-invasive method could also be of potential use in vivo for regenerative therapy of cartilage in the future.
Keywords: Chondrogenesis, stem cell, bone marrow, mechanobiology, ultrasound
Journal: Biorheology, vol. 43, no. 3-4, pp. 431-443, 2006
