Mesenchymal Stem Cells Regulate Angiogenesis According to Their Mechanical Environment

Kasper, Grit; Dankert, Niels; Tuischer, Jens; Hoeft, Moritz; Gaber, Timo; Glaeser, Juliane D.; Zander, Désirée; Tschirschmann, Miriam; Thompson, Mark S.; Matziolis, Georg; Duda, Georg N.

doi:10.1634/stemcells.2006-0432

Cited by 208 publications

(170 citation statements)

References 47 publications

(54 reference statements)

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“…42,43 Kasper et al showed that the conditioned medium from mesenchymal stem cells subjected to mechanical loading increased sprouting of endothelial cells by creating an angiogenic promoting environment. 44 Certainly other paracrine factors besides VEGF could also be playing a role in the improvement of cardiac function imparted by the MS MDSCs. For example, the conditioned medium of MS mesenchymal stem cells had an upregulation of MMP-2 and TGF-B1, 44 which is an area for future study.…”

Section: Discussionmentioning

confidence: 99%

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Mechanical Loading of Stem Cells for Improvement of Transplantation Outcome in a Model of Acute Myocardial Infarction: The Role of Loading History

Cassino

Drowley

Okada

et al. 2012

Tissue Engineering Part A

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Stem cell therapy for tissue repair is a rapidly evolving field and the factors that dictate the physiological responsiveness of stem cells remain under intense investigation. In this study we hypothesized that the mechanical loading history of muscle-derived stem cells (MDSCs) would significantly impact MDSC survival, host tissue angiogenesis, and myocardial function after MDSC transplantation into acutely infarcted myocardium. Mice with acute myocardial infarction by permanent left coronary artery ligation were injected with either nonstimulated (NS) or mechanically stimulated (MS) MDSCs. Mechanical stimulation consisted of stretching the cells with equibiaxial stretch with a magnitude of 10% and frequency of 0.5 Hz. MS cell-transplanted hearts showed improved cardiac contractility, increased numbers of host CD31 + cells, and decreased fibrosis, in the peri-infarct region, compared to the hearts treated with NS MDSCs. MS MDSCs displayed higher vascular endothelial growth factor expression than NS cells in vitro. These findings highlight an important role for cyclic mechanical loading preconditioning of donor MDSCs in optimizing MDSC transplantation for myocardial repair.

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Section: Discussionmentioning

confidence: 99%

“…44 Certainly other paracrine factors besides VEGF could also be playing a role in the improvement of cardiac function imparted by the MS MDSCs. For example, the conditioned medium of MS mesenchymal stem cells had an upregulation of MMP-2 and TGF-B1, 44 which is an area for future study.…”

Section: Discussionmentioning

confidence: 99%

Mechanical Loading of Stem Cells for Improvement of Transplantation Outcome in a Model of Acute Myocardial Infarction: The Role of Loading History

Cassino

Drowley

Okada

et al. 2012

Tissue Engineering Part A

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show abstract

“…For example, MSCs regulated angiogenesis according to their mechanical environment. Osteogenic proliferation and differentiation appeared when MSCs were stimulated by mechanical loading (Koike et al 2005;Yoshikawa et al 1997;Kasper et al 2007;Mauney et al 2004).…”

Section: Introductionmentioning

confidence: 99%

The simulated microgravity enhances multipotential differentiation capacity of bone marrow mesenchymal stem cells

Wang

Zhang

et al. 2013

Cytotechnology

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Multi-differentiation capability is an essential characteristic of bone marrow mesenchymal stem cells (BMSCs). Method on obtaining higherquality stem cells with an improved differentiation potential has gained significant attention for the treatment of clinical diseases and developmental biology. In our study, we investigated the multipotential differentiation capacity of BMSCs under simulated microgravity (SMG) condition. F-actin staining found that cytoskeleton took on a time-dependent change under SMG condition, which caused spindle to round morphological change of the cultured cells. Quantitative PCR and Western Blotting showed the pluripotency marker OCT4 was up-regulated in the SMG condition especially after SMG of 72 h, which we observed would be the most appropriate SMG duration for enhancing pluripotency of BMSCs. After dividing BMSCs into normal gravity (NG) group and SMG group, we induced them respectively in endothelium oriented, adipogenic and neuronal induction media. Immunostaining and Western Blotting found that endothelium oriented differentiated BMSCs expressed higher VWF and CD31 in the SMG group than in the NG group. The neuron-like cells derived from BMSCs in the SMG group also expressed higher level of MAP2 and NF-H. Furthermore, the quantity of induced adipocytes increased in the SMG group compared to the NG group shown by Oil Red O staining, The expression of PPARc2 increased significantly under SMG condition. Therefore, we demonstrated that SMG could promote BMSCs to differentiate into many kinds of cells and predicted that enhanced multi-potential differentiation capacity response in BMSCs following Electronic supplementary material The online version of this article

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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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Mesenchymal Stem Cells Regulate Angiogenesis According to Their Mechanical Environment

Abstract: The underlying mechanism appears to be dependent on the FGFR and VEGFR signaling cascades and might be mediated by an additional cross-talk with other pathways. STEM CELLS 2007;25:903-910 Disclosure of potential conflicts of interest is found at the end of this article.

Cited by 208 publications

References 47 publications

Mechanical Loading of Stem Cells for Improvement of Transplantation Outcome in a Model of Acute Myocardial Infarction: The Role of Loading History

Mechanical Loading of Stem Cells for Improvement of Transplantation Outcome in a Model of Acute Myocardial Infarction: The Role of Loading History

The simulated microgravity enhances multipotential differentiation capacity of bone marrow mesenchymal stem cells

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

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