Rüster, B, Göttig, S, Ludwig, RJ, Bistrian, R, Müller, S, Seifried, E et al.. Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells. Blood 108: 3938-3944

Paul-Ehrlich-Institut, Langen, Hesse, Germany
Blood (Impact Factor: 10.45). 01/2007; 108(12):3938-44. DOI: 10.1182/blood-2006-05-025098
Source: PubMed


To explore the initial steps by which transplanted mesenchymal stem cells (MSCs) interact with the vessel wall in the course of extravasation, we studied binding of human MSCs to endothelial cells (ECs). In a parallel plate flow chamber, MSCs bound to human umbilical vein ECs (HUVECs) similar to peripheral-blood mononuclear cells (PBMCs) or CD34(+) hematopoietic progenitors at shear stresses of up to 2 dynes/cm(2). This involved rapid extension of podia, rolling, and subsequent firm adhesion that was increased when ECs were prestimulated with TNF-alpha. MSC binding was suppressed when ECs were pretreated with function-blocking anti-P-selectin antibody, and rolling of MSCs was induced on immobilized P-selectin, indicating that P-selectin was involved in this process. Preincubation of HUVECs with anti-VCAM-1 or of MSCs with anti-VLA-4 antibodies suppressed binding of MSCs to HUVECs but did not enhance inhibition by anti-P-selectin, indicating that both P-selectin and VCAM-1 are equally required for this process. Intravital microscopy demonstrated the capacity of MSCs to roll and adhere to postcapillary venules in vivo in a mouse model in a P-selectin-dependent manner. Thus, MSCs interact in a coordinated fashion with ECs under shear flow, engaging P-selectin and VCAM-1/VLA-4.

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Available from: Ralf Joachim Ludwig, Oct 01, 2015
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    • "Stable vessels in vivo were achieved through the continuous release of VEGF from the scaffold [28]. VEGF functions as a potent angiogenic peptide, but the migration of BMSCs is also required for the formation of new vessels [29] [30]. The migration of cells to the site of injury is the foundation of the angiogenesis process. "
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    ABSTRACT: Our previous work showed that implanting a sensory nerve or vascular bundle when constructing vascularized and neurotized bone could promote bone osteogenesis in tissue engineering. This phenomenon could be explained by the regulatory function of neuropeptides. Neuropeptide substance P (SP) has been demonstrated to contribute to bone growth by stimulating the proliferation and differentiation of bone marrow stem cells (BMSCs). However, there have been no prior studies on the association between Wnt signaling and the mechanism of SP in the context of BMSC differentiation. Our results have shown that SP could enhance the differentiation of BMSCs by activating gene and protein expression via the Wnt pathway and by translocating β-catenin, which can be inhibited by Wnt signaling blocker treatment or by the NK-1 antagonist. SP could also increase the growth factor level of bone morphogenetic protein-2 (BMP-2). Additionally, SP could enhance the migration ability of BMSCs, and the promotion of vascular endothelial growth factor (VEGF) expression by SP has been studied. In conclusion, SP could induce osteoblastic differentiation via the Wnt pathway and promote the angiogenic ability of BMSCs. These results indicate that a vascularized and neurotized tissue-engineered construct could be feasible for use in bone tissue engineering strategies.
    BioMed Research International 06/2014; 2014:596023. DOI:10.1155/2014/596023 · 3.17 Impact Factor
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    • "Although there is no report about the expression of selectins in injured kidney after MSCs' treatment, P-selectin and its counter-ligand were found to be involved in the extravasation of MSCs [68]. Intravenously administered MSCs can roll along the walls of the blood vessels in the ear veins of mice, and this phenomenon was significantly decreased in mice genetically deficient of P-selectin. "
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    ABSTRACT: Acute kidney injury (AKI) remains to be an independent risk factor for mortality and morbidity. Inflammation is believed to play a major role in the pathophysiology of AKI. Exogenous mesenchymal stem cells (MSCs) are now under extensive investigation as a potential therapy for AKI. Various preclinical studies indicated the beneficial effects of MSCs in alleviating renal injury and accelerating tissue repair. However the mechanisms responsible for these effects are incompletely understood. In the recent years, anti-inflammatory/immunoregulatory properties of MSCs have become one of the important issues in the treatment of AKI. This review will summarize the current literature on the regulation of inflammatory mediators via exogenous MSCs contributing to the recovery from AKI.
    Mediators of Inflammation 04/2014; 2014(6):261697. DOI:10.1155/2014/261697 · 3.24 Impact Factor
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    • "Our previous study also showed that CXCR4 was involved in MSCs homing and engraftment to tumours, the migration potential of MSCs toward tumour cells was enhanced with the upregulation of CXCR4 when MSCs were exposed to tumour conditioned medium, and the SDF1 inhibitor, AMD3100, could partly abolish the MSCs migration toward tumour cells [18]. A big issue concerning the SDF1/CXCR4 axis is that CXCR4 is usually absent on the surface of MSCs culture-expanded in vitro [16] [19] [20]. To overcome this problem, stimulating the expression of CXCR4 is one of the strategies for enhancing the migration capacity of MSCs [21e23]. "
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    ABSTRACT: Circulating mesenchymal stem cells (MSCs) is a new cell source for tissue regeneration and tissue engineering. The characteristics of circulating MSCs are similar to those of bone marrow-derived MSCs (BM-MSCs), but they exist at a very low level in healthy individuals. It has been demonstrated that MSCs are able to migrate to the sites of injury and that they have some distinct genetic profiles compared to BM-MSCs. The current review summaries the basic knowledge of circulating MSCs and their potential clinical applications, such as mobilizing the BM-MSCs into circulation for therapy. The application of MSCs to cure a broad spectrum of diseases is promising, such as spinal cord injury, cardiovascular repair, bone and cartilage repair. The current review also discusses the issues of using of allogeneic MSCs for clinical therapy.
    01/2014; 2(1):1–7. DOI:10.1016/
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