Characterization of key mechanisms in transmigration and invasion of mesenchymal stem cells

Steingen, Caroline; Brenig, Florian; Baumgartner, Laura; Schmidt, Joachim; Schmidt, Annette; Bloch, Wilhelm

doi:10.1016/j.yjmcc.2008.03.010

Cited by 206 publications

(170 citation statements)

References 33 publications

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“…32 As shown in Figure 7, both anti-NCAM and anti-CD49d/VLA-4 reduced the adhesion of StCs. More specifically, anti-NCAM reduced the adhesion of HCC-StCs, nNL-StCs and Ad-StCs on quiescent Ld-MECs by 60%, 45% and 43% and by 72%, 56% and 55% on TNFa-activated Ld-MECs, respectively.…”

Section: Anti-ncam and Cd49d/vla-4 Antibodies Reduce Adhesion Of Stcsmentioning

confidence: 74%

Transforming growth factor-beta1 induces microvascular abnormalities through a down-modulation of neural cell adhesion molecule in human hepatocellular carcinoma

Balzarini

Benetti

Invernici

et al. 2012

Laboratory Investigation

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Hepatocellular carcinoma (HCC) is a very angiogenic and malignant cancer. Conventional chemotherapy is poorly effective because of the abnormal structural organization of HCC-infiltrating vessels. In previous work, we demonstrated that HCC angiogenesis is driven by transforming growth factor beta-1(TGF-b1)/CD105 axis, stimulating liver-derived microvascular endothelial cells (Ld-MECs) migration. As TGF-b1 also affects mural cells (MCs) recruitment and maturation, we asked whether it may contribute to HCC-induced vascular abnormalities. HCC and adjacent non-neoplastic liver (nNL) biopsies obtained from 12 patients were analyzed by immunohistochemistry for angiogenic markers CD105, TGF-b1, CD44 and vascular endothelial growth factor-a (VEGFa) and for MC markers NG2, a-smooth muscle actin (aSMA) and neural cell adhesion molecule (NCAM). The same markers were also investigated by immunocytochemistry on cultured HCC-derived stromal cells (HCC-StCs) and nNL-derived StCs (nNL-StCs) isolated from the same liver biopsies. Angiogenic factors released by StCs were analyzed by ELISA and the interaction between StCs and Ld-MECs by adhesion assay. Compared with nNL, HCC biopsies showed increased angiogenic markers and aSMA that was localized in vessels. By contrast, NG2 and NCAM were substantially localized in tumor cells but absent in vessels and stroma. Cultured HCCStCs showed less expression of NG2, aSMA and NCAM. They also demonstrated a lower capacity to release angiogenic factors and adhered on Ld-MECs. HCC-StCs and nNL-StCs treated with TGF-b1 or with of HepG2 (a human hepatoma cell line) derived conditioned medium (CM), down-modulated NCAM expression, whereas anti-NCAM antibodies significantly reduced the adhesion of StCs to Ld-MECs. By further blocking TGF-b1 with anti-TGF-b1 antibodies or with Ly-364947 (a specific inhibitor TGF-b1-receptor) adhesion to Ld-MECs and NCAM expression respectively was partially restored. TGF-b1 contributes to HCC-induced vascular alterations by affecting the interaction between HCC-StCs and Ld-MECs through a down-modulation of NCAM expression. A growing tumor recruits new blood vessels to ensure a sufficient quantity of nutrients and oxygen necessary for cancer cell survival and proliferation.1 During this process, neoformed capillaries undergo abnormal maturation 2 and vascular abnormalities are often observed in tumor, mainly involving either the composition of the basement membrane or mural cells (MCs) content. 3,4 To this regard, pericytes and smooth muscle cells (SMCs) are fundamental to determine an

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Section: Anti-ncam and Cd49d/vla-4 Antibodies Reduce Adhesion Of Stcsmentioning

confidence: 74%

Transforming growth factor-beta1 induces microvascular abnormalities through a down-modulation of neural cell adhesion molecule in human hepatocellular carcinoma

Balzarini

Benetti

Invernici

et al. 2012

Laboratory Investigation

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“…61 Furthermore, it was reported that MSCs can transmigrate through non-activated endothelial monolayers via VCAM-1/VLA-4 interactions, in addition to MMP-2 secretion and by other interactions with various integrins and cytokines, and possibly integrate with the endothelial layer as embedded pericytes. 63 Future studies are required to discover more similarities and differences of MSC and HSC homing mechanisms.…”

Section: Sdf-1/cxcr4 Axis and Bone Formationmentioning

confidence: 99%

Modulation of Stromal Cell-Derived Factor-1/CXC Chemokine Receptor 4 Axis Enhances rhBMP-2-Induced Ectopic Bone Formation

Wise

Sumner²,

Virdi³

2012

Tissue Engineering Part A

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Enhancement of in vivo mobilization and homing of endogenous mesenchymal stem cells (MSCs) to an injury site is an innovative strategy for improvement of bone tissue engineering and repair. The present study was designed to determine whether mobilization by AMD3100 and/or local homing by delivery of stromal cellderived factor-1 (SDF-1) enhances recombinant human bone morphogenetic protein-2 (rhBMP-2) induced ectopic bone formation in an established rat model. Rats received an injection of either saline or AMD3100 treatment 1 h before harvesting of bone marrow for in vitro colony-forming unit-fibroblasts (CFU-F) culture or the in vivo subcutaneous implantation of absorbable collagen sponges (ACSs) loaded with saline, recombinant human bone morphogenetic protein-2 (rhBMP-2), SDF-1, or the combination of SDF-1 and rhBMP-2. AMD3100 treatment resulted in a significant decrease in CFU-F number, compared with saline, which confirmed that a single systemic AMD3100 treatment rapidly mobilized MSCs from the bone marrow. At 28 and 56 days, bone formation in the explanted ACS was assessed by microcomputed tomography (mCT) and histology. At 28 days, AMD3100 and/or SDF-1 had no statistically significant effect on bone volume (BV) or bone mineral content (BMC), but histology revealed more active bone formation with treatment of AMD3100, loading of SDF-1, or the combination of both AMD3100 and SDF-1, compared with saline-treated rhBMP-2 loaded ACS. At 56 days, the addition of AMD3100 treatment, loading of SDF-1, or the combination of both resulted in a statistically significant stimulatory effect on BV and BMC, compared with the saline-treated rhBMP-2 loaded ACS. Histology of the 56-day ACS were consistent with the mCT analysis, exhibiting more mature and mineralized bone formation with AMD3100 treatment, SDF-1 loading, or the combination of both, compared with the saline-treated rhBMP-2 loaded ACS. The present study is the first that provides evidence of the efficacy of AMD3100 and SDF-1 treatment to stimulate trafficking of MSCs to an ectopic implant site, in order to ultimately enhance rhBMP-2 induced long-term bone formation.

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“…The ability of MSC to cross the basement membrane was evaluated using a surrogate basement membrane (collagen gel) followed by a Collagen Invasion Assay [9]. Briefly,…”

Section: Trans-collagen Invasion Assaymentioning

confidence: 99%

“…increased barrier to engraftment and survival of mobilized MSC, as its degradation via proteolytic enzymes is a prerequisite for the invasion of MSC [9]. Small new vessel formation in a collagen-containing fibrin matrix is largely driven by MMPs; specifically by membrane-type metalloproteinase(s) [6].…”

Section: Msc Cx4 Release Anti-fibrotic Enzymesmentioning

confidence: 99%

“…The migration to injured tissue sites can be blocked by an MMP inhibitor derived from green tea (Camellia sinensis); polyphenol epigallocatechin-3-gallate (EGCG) [9]. This evidence further implicates the role of MMPs in MSC migration, although the involvement of other specific MMPs cannot be ruled out [9]. The MMP-9 is associated with increased CXCR4 expression in CD34…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal Stem Cells Overexpressing CXCR4 Attenuate Remodeling of Postmyocardial Infarction by Releasing Matrix Metalloproteinase-9

Huang

Wang

Zhang

et al. 2012

Stem Cells and Development

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Myocardial infarction (MI) results in loss of myofibers in the ischemic zone of the heart, followed by scar formation. These factors increase barriers to mobilization of mesenchymal stem cells (MSC), thereby impeding their effectiveness in cardiac repair. This study examined MSC overexpressing CXCR4 (MSC CX4 ) to determine penetration into infarcted myocardium by releasing collagen degrading enzyme, matrix metalloproteinase-9 (MMP-9). In vitro, mouse MSC were utilized, including MSC using adenoviral transduction, to express CXCR4/ green fluorescent protein (GFP) (MSC CX4 ), Null/GFP (MSC Null ), MSC treated with siRNA targeting CXCR4 (MSC siR ), MSC treated with control siRNA(MSC Con-siR ), MSC CX4 treated with siRNA targeting MMP-9 (MSC CX4-siRMP9 ) and MMP-14 (MSC CX4-siRMP14 ), MSC derived from MMP-9 knockout mouse with adenoviral transduction for GFP (MSC MP9 -), or MSC MP9 -plus overexpressing CXCR4 (MSC MP9-CX4 ). The ability to cross the basement membrane was evaluated in all MSC using a trans-collagen gel invasion assay. The CXCR4 and MMP expression were analyzed by Western blot. In vivo, MSC with various treatments were infused into mice via tail vein injections 7 days after MI. Echocardiography was performed before harvesting hearts for analysis at 4 weeks after MSC injection. Both in vitro and in vivo studies demonstrated upregulation of MMP-9 induced by MSC CX4 , promoting increased GFP + cell migration into the infarcted area in comparison to control group. This enhanced response was associated with reduced left ventricular (LV) fibrosis, increased LV free wall thickness, angiogenesis, and improved LV function. Under hypoxic conditions, MMP-9 is upregulated in MSC CX4 , thus facilitating cross of the basement membrane, resulting in an improved remodeling of post-MI tissue.

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Characterization of key mechanisms in transmigration and invasion of mesenchymal stem cells

Cited by 206 publications

References 33 publications

Transforming growth factor-beta1 induces microvascular abnormalities through a down-modulation of neural cell adhesion molecule in human hepatocellular carcinoma

Transforming growth factor-beta1 induces microvascular abnormalities through a down-modulation of neural cell adhesion molecule in human hepatocellular carcinoma

Modulation of Stromal Cell-Derived Factor-1/CXC Chemokine Receptor 4 Axis Enhances rhBMP-2-Induced Ectopic Bone Formation

Mesenchymal Stem Cells Overexpressing CXCR4 Attenuate Remodeling of Postmyocardial Infarction by Releasing Matrix Metalloproteinase-9

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