Matrix Metalloprotease Activity Is an Essential Link Between Mechanical Stimulus and Mesenchymal Stem Cell Behavior

Kasper, Grit; Glaeser, Juliane D.; Geißler, Sven; Ode, Andrea; Tuischer, Jens; Matziolis, Georg; Perka, Carsten; Duda, Georg N.

doi:10.1634/stemcells.2006-0676

Cited by 108 publications

(77 citation statements)

References 62 publications

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“…Importantly, the latter condition likely affects MSCs, which are known to be mechanosensitive (Wang and Thampatty, 2008). Thus, detailed knowledge about the infl uence of mechanical loading on MSCs is pivotal for understanding (Kasper et al, 2007a) and matrix remodelling (Kasper et al, 2007b) -key processes in bone regeneration. However, investigations regarding cell autonomous alterations in MSCs, specifi cally their MSC-characteristics and associated functional changes due to loading are still missing.…”

Section: Introductionmentioning

confidence: 99%

CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory capacity of mesenchymal stromal cells

Ode

Kopf²,

Kurtz³

et al. 2011

eCM

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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.

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Section: Introductionmentioning

confidence: 99%

CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory capacity of mesenchymal stromal cells

Ode

Kopf²,

Kurtz³

et al. 2011

eCM

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“…Treg cells are essential in the everyday control of immune responses and maintaining peripheral tolerance [6,7]. Two populations of T regs control inflammation: natural (constitutive) Treg cells and induced Treg cells (iT reg ) (Figure 2.3).…”

Section: T Cellsmentioning

confidence: 99%

Principles of Immunotherapy

Joscelyn¹,

Kasper²

2011

Clinical Neuroimmunology

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“…Im Kern steht die Hypothese, dass sowohl mechanische als auch biologische Rahmenbedingungen die Heilung des Knochens maßgeblich beeinflussen [5,6,7,8,9]. Die Art des Heilungsprozesses, insbesondere auch seine Geschwindigkeit, wird durch diese Rahmenbedingungen beeinflusst.…”

Section: Forschung Zum Intakten Und Verletzten Knochenunclassified

Clinical research in partnership

Duda

Benusch

Haas

2010

Chirurg

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As a result of the demographic development of industrial nations the number of musculoskeletal diseases and injuries rises continuously. This challenges health care as well as clinical research and demands additional endeavours. The United Nations have recognised this issue at an early stage. With their in 2000 declared Bone and Joint Decade they have significantly contributed to a sustainable support of research activities. The German government has also perceived the need and, with their roadmap programme, encourages research of musculoskeletal disease.Today, surgical and orthopaedic clinics increasingly support the exchange between research and clinic and run their own research departments. The Berlin Center for Musculoskeletal Surgery (CMSC) and its research institute Julius Wolff Institut show the potential for surgical research. It shows that based on a clinical understanding of the problem, basic research needs to be complemented in a network with partners from other disciplines. However, interdisciplinary cooperation demands new and individual ways of communication and education. The example in Berlin also illustrates that the research on prevention not only completes the network but more over opens unexpected possibilities in understanding basic research and translation.

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Matrix Metalloprotease Activity Is an Essential Link Between Mechanical Stimulus and Mesenchymal Stem Cell Behavior

Cited by 108 publications

References 62 publications

CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory capacity of mesenchymal stromal cells

CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory capacity of mesenchymal stromal cells

Principles of Immunotherapy

Clinical research in partnership

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