CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory capacity of mesenchymal stromal cells
| Autor: | Paula Kolar, Georg N. Duda, Andreas Kurtz, Petra Schrade, Dietmar W. Hutmacher, Andrea Ode, Frank Buttgereit, Kai Lehmann, Katharina Schmidt-Bleek, Jessica Kopf, Grit Kasper |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
CD29
lcsh:Diseases of the musculoskeletal system Stromal cell Phalloidin lcsh:Surgery Down-Regulation Stimulation GPI-Linked Proteins migration Focal adhesion Fractures Bone chemistry.chemical_compound Cell Movement Humans Regeneration mechanical stimulation 5'-Nucleotidase Cells Cultured Actin Fracture Healing Wound Healing Integrin beta1 Mesenchymal stem cell Mesenchymal Stem Cells cytoskeleton lcsh:RD1-811 Biomechanical Phenomena Cell biology chemistry Immunology CD73 lcsh:RC925-935 Lamellipodium mesenchymal stromal cells |
| Zdroj: | European Cells & Materials, Vol 22, Pp 26-42 (2011) Scopus-Elsevier |
| Popis: | The assumption that mesenchymal stromal cell (MSC)based-therapies are capable of augmenting physiological regeneration processes has fostered intensive basic and clinical research activities. However, to achieve sustained therapeutic success in vivo, not only the biological, but also the mechanical microenvironment of MSCs during these regeneration processes needs to be taken into account. This is especially important for e.g., bone fracture repair, since MSCs present at the fracture site undergo signifi cant biomechanical stimulation. This study has therefore investigated cellular characteristics and the functional behaviour of MSCs in response to mechanical loading. Our results demonstrated a reduced expression of MSC surface markers CD73 (ecto-5’-nucleotidase) and CD29 (integrin β1) after loading. On the functional level, loading led to a reduced migration of MSCs. Both effects persisted for a week after the removal of the loading stimulus. Specifi c inhibition of CD73/CD29 demonstrated their substrate dependent involvement in MSC migration after loading. These results were supported by scanning electron microscopy images and phalloidin staining of actin fi laments displaying less cell spreading, lamellipodia formation and actin accumulations. Moreover, focal adhesion kinase and Src-family kinases were identifi ed as candidate downstream targets of CD73/CD29 that might contribute to the mechanically induced decrease in MSC migration. These results suggest that MSC migration is controlled by CD73/CD29, which in turn are regulated by mechanical stimulation of cells. We therefore speculate that MSCs migrate into the fracture site, become mechanically entrapped, and thereby accumulate to fulfi l their regenerative functions. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|