Mesenchymal Stem Cells and the Artery Wall

Abedin, Moeen; Tintut, Yin; Demer, Linda L.

doi:10.1161/01.res.0000143421.27684.12

Cited by 201 publications

(140 citation statements)

References 106 publications

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“…Recent studies suggest that bone marrow-derived MSC account for about 20% of osteochondrogenic (Runx-2/Cbfa1)-positive cells in calcified atherosclerotic vessels of ApoE -/ -mice, whereas VSMC were found to be a major contributor to vascular calcification reprogramming its lineage toward osteogenic differentiation [12]. Further reports provide evidence that ECs may also participate in vascular calcification [49] and that MSC serve as the main source for both VSMC and EC in atherosclerotic plaques [50]. Our findings could be explained in several ways.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…tem cell transplantation has shown increasing therapeutic potential for treatment of pathological situations tissue restoration [1][2][3]. Mesenchymal stem cells (MSCs), the stromal progenitor cells found in the bone marrow [3], were recently proved effective in vascular enhancement and protection [4,5].…”

mentioning

confidence: 99%

Transcriptional Profiling Reveals Crosstalk Between Mesenchymal Stem Cells and Endothelial Cells Promoting Prevascularization by Reciprocal Mechanisms

LiJunxiang

MaYing

TengRuifang

et al. 2015

Stem Cells and Development

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Mesenchymal stem cells (MSCs) show great promise in blood vessel restoration and vascularization enhancement in many therapeutic situations. Typically, the co-implantation of MSCs with vascular endothelial cells (ECs) is effective for the induction of functional vascularization in vivo, indicating its potential applications in regenerative medicine. The effects of MSCs-ECs-induced vascularization can be modeled in vitro, providing simplified models for understanding their underlying communication. In this article, a contact coculture model in vitro and an RNA-seq approach were employed to reveal the active crosstalk between MSCs and ECs within a short time period at both morphological and transcriptional levels. The RNA-seq results suggested that angiogenic genes were significantly induced upon coculture, and this prevascularization commitment might require the NF-kB signaling. NF-kB blocking and interleukin (IL) neutralization experiments demonstrated that MSCs potentially secreted IL factors including IL1b and IL6 to modulate NF-kB signaling and downstream chemokines during coculture. Conversely, RNA-seq results indicated that the MSCs were regulated by the coculture environment to a smooth muscle commitment within this short period, which largely induced myocardin, the myogenic co-transcriptional factor. These findings demonstrate the mutual molecular mechanism of MSCs-ECs-induced prevascularization commitment in a quick response.

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“…These extramarrow MSCs are similar to bone marrow-derived stem cells, which can differentiate into different various cell lineages. MSCs may also be found in the arterial wall 11 and may contribute to the bone formation in ectopic tissue. These MSCs also may enter the circulation, contributing to the population of circulating progenitor cells and engrafting other tissue.…”

Section: Discussionmentioning

confidence: 99%

Bone Formation in Elastase-Induced Rabbit Aneurysms Embolized with Platinum Coils: Report of 2 Cases

Dai

Ding

Kadirvel³

et al. 2007

American Journal of Neuroradiology

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SUMMARY:Histologic findings in 71 elastase-induced rabbit aneurysms embolized with platinum coils were retrospectively reviewed. Mature bone formation was found in 2 aneurysms, one with coils implanted for 3 months and the other with coils implanted for 1 year. We present the histologic findings and offer potential explanations for these observations. These findings may be relevant in understanding mechanisms of aneurysm healing after coil embolization.

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Mesenchymal Stem Cells and the Artery Wall

Cited by 201 publications

References 106 publications

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

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

Transcriptional Profiling Reveals Crosstalk Between Mesenchymal Stem Cells and Endothelial Cells Promoting Prevascularization by Reciprocal Mechanisms

Bone Formation in Elastase-Induced Rabbit Aneurysms Embolized with Platinum Coils: Report of 2 Cases

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