Differential regulation of smooth muscle markers in human bone marrow-derived mesenchymal stem cells

Hegner, Björn; Weber, Manfred; Dragun, Duska; Schulze-Lohoff, Eckhard

doi:10.1097/01.hjh.0000170382.31085.5d

Cited by 69 publications

(71 citation statements)

References 43 publications

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“…In HuF cells, changes in cells induced by DMSO are connected with a loss of α-SMA, the short isoform of MLCK, and calponin, while β-actin and vimentin remain in uniform amounts. A similar transition to a less differentiated state after DMSO treatment was described in myofibroblasts originating from bone-marrow derived MSC with mTOR suggested as a participant in the transition regulation (Hegner et al 2005). It was proposed that regulating the phenotype of human MSCs may be of relevance for novel therapeutic approaches in arterosclerosis and intimal hyperplasia after vascular injury (Hegner et al 2005).…”

Section: Discussionmentioning

confidence: 82%

Multipotent properties of myofibroblast cells derived from human placenta

et al. 2008

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Human uterine fibroblasts (HuF) isolated from the maternal part (decidua parietalis) of a term placenta provide a useful model of in vitro cell differentiation into decidual cells (decidualization), critical for successful pregnancy. After isolation, the cells adhere to plastic and have either a small round or spindle-shaped morphology which later changes into a flattened pattern in culture. HuF robustly proliferate in culture until passage 20 and form colonies when plated at low densities. The cells express the mesenchymal cell markers fibronectin, integrin-β1, ICAM-1 (CD54), and collagen I. Flow cytometry of HuF detected the presence of CD34, a marker of hematopoietic stem cell lineage, and an absence of CD10, CD11b/Mac, CD14, CD45, and HLA type II. Furthermore, they also express the pluripotency markers SSEA-1, SSEA-4, Oct-4, Stro-1, and TRA-1−81 as detected by confocal microscopy. Treatment for 14−21 days with differentiation-inducing media led to the differentiation of HuF into osteoblasts, adipocytes, and chondrocytes. The presence of α-smooth muscle actin, calponin, and myosin light chain kinase in cultured HuF implies their similarity to myofibroblasts. Treatment of the HuF with DMSO causes reversion back into the spindle-shaped morphology and a loss of myofibroblast characteristics, suggesting a switch into a less differentiated phenotype. The unique abilities of HuF to exhibit multipotency, even with myofibroblast characteristics, and their ready availability and low maintenance requirements make them an interesting cell model for further exploration as a possible tool for regenerative medicine.

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Section: Discussionmentioning

confidence: 82%

Multipotent properties of myofibroblast cells derived from human placenta

et al. 2008

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“…MSC are multipotent progenitor cells with the capacity to differentiate into different tissue cell types, such as chondrocytes, osteocytes, adipocytes, and VSMC-like cells [17][18][19][20][21][22]. To address the question of a probable involvement of C5aR and uPAR in MSC osteogenic differentiation, experimental conditions for this process have been first established.…”

Section: Msc Undergo Differentiation To Osteoblastsmentioning

confidence: 99%

Urokinase Receptor Mediates Osteogenic Differentiation of Mesenchymal Stem Cells and Vascular Calcification via the Complement C5a Receptor

Anaraki

Patecki²,

Larmann³

et al. 2014

Stem Cells and Development

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Vascular calcification is a severe consequence of several pathological processes with a lack of effective therapy. Recent studies suggest that circulating and resident mesenchymal stem cells (MSC) contribute to the osteogenic program of vascular calcification. Molecular mechanisms underlying MSC osteogenic potential and differentiation remain, however, sparsely explored. We investigated a role for the complement receptor C5aR in these processes. We found that expression of C5aR was upregulated upon differentiation of human MSC to osteoblasts. C5aR inhibition by silencing and specific antagonist impaired osteogenic differentiation. We demonstrate that C5aR expression upon MSC differentiation was regulated by the multifunctional urokinase receptor (uPAR). uPAR targeting by siRNA resulted in complete abrogation of C5aR expression and consequently in the inhibition of MSC-osteoblast differentiation. We elucidated the NFkB pathway as the mechanism utilized by the uPAR-C5aR axis. MSC treatment with the NFkB inhibitor completely blocked the differentiation process. Nuclear translocation of the p65 RelA component of the NFkB complex was induced under osteogenic conditions and impaired by the inhibition of uPAR or C5aR. Dual-luciferase reporter assays demonstrated enhanced NFkB signaling upon MSC differentiation, whereas uPAR and C5aR downregulation lead to inhibition of the NFkB activity. We show involvement of the Erk1/2 kinase in this cascade. In vivo studies in a uPAR/LDLR double knockout mouse model of diet-induced atherosclerosis revealed impaired C5aR expression and calcification in aortic sinus plaques in uPAR -/ -/LDLR -/ -versus uPAR + / + /LDLR -/ -control animals. These results suggest that uPAR-C5aR axis via the underlying NFkB transcriptional program controls osteogenic differentiation with functional impact on vascular calcification in vivo.

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“…They contribute to the regeneration of mesenchymal tissues and, when grown in appropriate conditions in vitro, classically differentiate into osteoblasts, chondrocytes, or adipocytes [19]. Resting MSC with multilineage differentiation potential express smooth muscle- specific contractile proteins and functional L-type Cav1.2 Ca2þ channels, which represent specific markers of differentiated vascular smooth muscle cells [20][21][22]. In a wireinduced vascular injury model, MSC have a strong capacity of adherence to injured vessels [22,23] and contribute to neointima formation as well as vascular remodeling [22].…”

Section: Introductionmentioning

confidence: 99%

Epidermal Growth Factor and Perlecan Fragments Produced by Apoptotic Endothelial Cells Co-Ordinately Activate ERK1/2-Dependent Antiapoptotic Pathways in Mesenchymal Stem Cells

et al. 2010

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Mounting evidence indicates that mesenchymal stem cells (MSC) are pivotal to vascular repair and neointima formation in various forms of vascular disease. Yet, the mechanisms that allow MSC to resist apoptosis at sites where other cell types, such as endothelial cells (EC), are dying are not well defined. In the present work, we demonstrate that apoptotic EC actively release paracrine mediators which, in turn, inhibit apoptosis of MSC. Serum-free medium conditioned by apoptotic EC increases extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation and inhibits apoptosis (evaluated by Bcl-xL protein levels and poly (ADP-ribose) polymerase cleavage) of human MSC. A C-terminal fragment of perlecan (LG3) released by apoptotic EC is one of the mediators activating this antiapoptotic response in MSC.LG3 interacts with b1-integrins, which triggers downstream ERK1/2 activation in MSC, albeit to a lesser degree than medium conditioned by apoptotic EC. Hence, other mediators released by apoptotic EC are probably required for induction of the full antiapoptotic phenotype in MSC. Adopting a comparative proteomic strategy, we identified epidermal growth factor (EGF) as a novel mediator of the paracrine component of the endothelial apoptotic program.LG3 and EGF cooperate in triggering b1-integrin and EGF receptor-dependent antiapoptotic signals in MSC centering on ERK1/2 activation. The present work, providing novel insights into the mechanisms facilitating the survival of MSC in a hostile environment, identifies EGF and LG3 released by apoptotic EC as central antiapoptotic mediators involved in this paracrine response. STEM CELLS 2010;28:810-820 Disclosure of potential conflicts of interest is found at the end of this article.

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Differential regulation of smooth muscle markers in human bone marrow-derived mesenchymal stem cells

Cited by 69 publications

References 43 publications

Multipotent properties of myofibroblast cells derived from human placenta

Multipotent properties of myofibroblast cells derived from human placenta

Urokinase Receptor Mediates Osteogenic Differentiation of Mesenchymal Stem Cells and Vascular Calcification via the Complement C5a Receptor

Epidermal Growth Factor and Perlecan Fragments Produced by Apoptotic Endothelial Cells Co-Ordinately Activate ERK1/2-Dependent Antiapoptotic Pathways in Mesenchymal Stem Cells

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