CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory capacity of mesenchymal stromal cells
Ode, A. , Kurtz, A. , Schmidt-Bleek, K. , Schrade, P. , Kolar, P. , Buttgereit, F. , Lehmann, K. , Hutmacher, D.W., Duda, G.N. , & Kasper, G. (2011) CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory capacity of mesenchymal stromal cells. European Cells and Materials, 22, pp. 26-42.
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 significant 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 identified 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 fulfil their regenerative functions.
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|Item Type:||Journal Article|
|Keywords:||CD29, CD73 , cytoskeleton , mechanical stimulation, mesenchymal stromal cells|
|Subjects:||Australian and New Zealand Standard Research Classification > ENGINEERING (090000) > BIOMEDICAL ENGINEERING (090300) > Biomaterials (090301)|
|Divisions:||Past > QUT Faculties & Divisions > Faculty of Built Environment and Engineering|
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2011 The Authors|
|Copyright Statement:||Reproduced with eCM journal (www.ecmjournal.org). Founded by scientists for the benefit of Science rather than profit.|
|Deposited On:||19 Jul 2011 08:47|
|Last Modified:||24 Aug 2012 08:21|
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