title: CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory capacity of mesenchymal stromal cells.
abstract: e 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. Specific 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 filaments 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.
authors: Julius Wolff Institute and Musculoskeletal Research Center Berlin, Charité-Universitätsmedizin, Berlin, Germany.
authors: A
authors: A
authors: Ode
authors: J
authors: J
authors: Kopf
authors: A
authors: A
authors: Kurtz
authors: K
authors: K
authors: Schmidt-Bleek
authors: P
authors: P
authors: Schrade
authors: P
authors: P
authors: Kolar
authors: F
authors: F
authors: Buttgereit
authors: K
authors: K
authors: Lehmann
authors: D W
authors: DW
authors: Hutmacher
authors: G N
authors: GN
authors: Duda
authors: G
authors: G
authors: Kasper
mesh_terms: D015720:5'-Nucleotidase / Q000502:physiology*; D001696:Biomechanical Phenomena; D002465:Cell Movement; D002478:Cells, Cultured; D015536:Down-Regulation; D017102:Fracture Healing; D050723:Fractures, Bone / Q000628:therapy; D058851:GPI-Linked Proteins / Q000502:physiology; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D012038:Regeneration; D014945:Wound Healing
chemical_list: D058851:GPI-Linked Proteins; D019012:Integrin beta1; D015720:5'-Nucleotidase; C548241:NT5E protein, human