Transfer of Bone-Marrow-Derived Mesenchymal Stem Cells Influences Vascular Remodeling and Calcification after Balloon Injury in Hyperlipidemic Rats

Liao, Jianquan; Chen, Xiaochun; Li, Yongdong; Zhang, Ge; Duan, Hongyu; Zou, Yunzeng; Ge, Junbo

doi:10.1155/2012/165296

Cited by 32 publications

(29 citation statements)

References 17 publications

(20 reference statements)

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“…It has been documented that MSC therapy is related to the development of atherosclerosis. In particular, it was shown recently that transplantation of bone marrow-derived MSC induced vascular remodeling and calcification after balloon angioplasty in hyperlipidemic rats [52]. Another previous study showed increased size of atherosclerotic lesion as a result of MSC homing [53].…”

Section: Discussionmentioning

confidence: 98%

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: 98%

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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show abstract

“…Inward remodeling might also contribute to restenosis [ 2 ]. Some studies have shown that MSCs can improve vascular remodeling and prevent neointimal formation [ 9 – 17 , 19 , 20 ], while other studies found that MSCs increase neointimal formation and aggravate vascular remodeling [ 8 , 18 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

Meta-Analysis of the Effect of Mesenchymal Stem Cell Transplantation on Vascular Remodeling after Carotid Balloon Injury in Animal Models

Zou

Liu

et al. 2015

PLoS ONE

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AimA meta-analysis was conducted to assess the efficacy of mesenchymal stem cell (MSC) transplantation in small animal coronary vessels after balloon injury, to provide data for the design of future pre-clinical experiments and human clinical trials.MethodsThe search strategy included the PubMed, EMBASE, Chinese Biomedical Literature (CBM), and China National Knowledge Infrastructure (CKNI) databases. The endpoint was the ratio of vascular neointima/media (I/M). Moreover, neointimal area, re-endothelialization, and proliferating cell nuclear antigen (PCNA) expression were analyzed. Pooled analyses were conducted using random effects models. Heterogeneity and publication bias were also explored. All data were analyzed using RevMan 5.2 and Stata 12.0.ResultsFifteen studies were reviewed from 238 retrieved animal studies. Compared with controls, MSC transplantation resulted in greater I/M reduction (pooled difference, 0.39; 95% CI, 0.57–0.21; P < 0.0001), greater neointimal area reduction (pooled difference, 0.16; 95% CI, 0.22–0.10; P < 0.0001), decreased PCNA expression (pooled difference, 17.69; 95% CI, 28.94–6.44; P = 0.002), and enhanced re-endothelialization (pooled difference, 3.37; 95% CI, 1.78–4.95; P < 0.0001). The multivariable meta-regression analysis showed that a higher number of transplanted cells (>106; P = 0.017) and later time point of I/M measurement (P = 0.022) were significantly associated with I/M reduction. Subgroup analysis demonstrated a trend for a greater reduction in the ratio of I/M with late MSC transplantation (>1 day), MSCs transplanted through intravenous injection, and atherosclerotic vessels.ConclusionThe meta-analysis results demonstrate that MSC transplantation might improve injured vascular remodeling. In addition to greater efficacy with a greater number of transplanted MSCs (>106), the long-term effect of MSC transplantation appears to be more significant. The findings of this meta-analysis may help to design future, effective MSC trials.

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“…Adipose tissue derived MSCs are reported to primarily undergo osteogenic and chondrogenic differentiation in vivo, which might result in formation of undesirable cell types in target tissues leading to other pathological changes such as cyst formation or tissue calcification. Additionally, modified LDL and free cholesterol are potent inducers of MSC migration and differentiation, which may cause harmful changes such as vascular calcification, inflammation and vascular remodeling [63,64]. Several studies also suggest that adipose tissue derived MSCs and BM-MSCs retain an ability to facilitate tumorigenesis [65][66][67].…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Mesenchymal Stem Cells: A Potential Promise in Treating Atherosclerosis?

Zhang¹,

Wang²,

Colello³

et al. 2018

Preprint

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Atherosclerosis is a chronic inflammatory disease which results in thickening of the vessel wall and narrowing of the lumen. It is a leading cause of death worldwide. Preventive treatment is taken into prioritized consideration since currently no effective approaches to cure atherosclerosis are available. These treatments mainly focus on lowering blood cholesterol levels, especially LDL-C, by statins. Even so, lowering lipid levels is not sufficient to reduce the risk of cardiovascular events in all patients. Recently, atherosclerosis has increasingly been recognized as a chronic inflammatory disease involving the immune system, initiating new therapeutic approaches which could alleviate or prevent atherosclerosis by modulating inflammation. Mesenchymal stem cells (MSCs) have emerged as a promising option to relieve inflammation and balance immune responses in inflammatory diseases. Several studies including our group also reported that MSCs may be a new therapeutic option for atherosclerosis. This review summarizes the updated state of our knowledge in the administration of MSCs to alleviate atherosclerosis and discusses some of the key unresolved challenges that need to be solved in future studies.

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Transfer of Bone-Marrow-Derived Mesenchymal Stem Cells Influences Vascular Remodeling and Calcification after Balloon Injury in Hyperlipidemic Rats

Cited by 32 publications

References 17 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

Meta-Analysis of the Effect of Mesenchymal Stem Cell Transplantation on Vascular Remodeling after Carotid Balloon Injury in Animal Models

Mesenchymal Stem Cells: A Potential Promise in Treating Atherosclerosis?

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