Endothelial-like cells differentiated from mesenchymal stem cells attenuate neointimal hyperplasia after vascular injury

Xu, Jianzhong; Wu, Duojiao; Yang, Yan; Ji, Kaida; Gao, Pingjin

doi:10.3892/mmr.2016.5799

Cited by 13 publications

(14 citation statements)

References 25 publications

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“…Neointimal formation was attenuated by MSC transplantation in balloon-induced arterial injury models, which was associated with enhanced endothelial repair [ 10 , 11 ]. Moreover, transplantation of endothelial-like cells derived from MSCs preferably suppressed intimal hyperplasia following vascular injury [ 12 ]. This suggested that MSCs attenuated arteriosclerosis at least partly via endothelial regeneration.…”

Section: Introductionmentioning

confidence: 99%

The differentiation of mesenchymal stem cells to vascular cells regulated by the HMGB1/RAGE axis: its application in cell therapy for transplant arteriosclerosis

Meng

Chen

et al. 2018

Stem Cell Res Ther

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BackgroundMesenchymal stem cell (MSC) transplantation shows promise for treating transplant arteriosclerosis, at least partly via promoting endothelial regeneration. However, the efficacy and safety are still under investigation especially regarding recent findings that neointimal smooth muscle cells are derived from MSC-like cells. The high mobility group box 1 (HMGB1)/receptor for advanced glycation end-product (RAGE) axis is involved in regulating proliferation, migration, and differentiation of MSCs, and therefore it can be presumably applied to improve the outcome of cell therapy. The aim of the current study was to investigate this hypothesis.MethodsRat MSCs were treated with HMGB1 or modified with HMGB1 vectors to activate the HMGB1/RAGE axis. RAGE was targeted and inhibited by specific short hairpin RNA vectors. We assessed the capacity for cell proliferation, migration, and differentiation after vector transfection in vitro and in a rat model of transplant arteriosclerosis. The expression of CD31 and α-smooth muscle actin (αSMA) was determined to evaluate the differentiation of MSCs to endothelial cells and smooth muscle cells.ResultsExogenous HMGB1 treatment and transfection with HMGB1 vectors promoted MSC migration and vascular endothelial growth factor (VEGF)-induced differentiation to CD31+ cells while inhibiting their proliferation and platelet-derived growth factor (PDGF)-induced differentiation to αSMA+ cells. Such an effect was blocked by RAGE knockdown. HMGB1-modified cells preferably migrated to graft neointima and differentiated to CD31+ cells along with significant relief of transplant arteriosclerosis and inhibition of HMGB1 and RAGE expression in graft vessels. RAGE knockdown inhibited cell migration to graft vessels.ConclusionsHMGB1 stimulated MSCs to migrate and differentiate to endothelial cells via RAGE signaling, which we translated to successful application in cell therapy for transplant arteriosclerosis.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0827-z) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

The differentiation of mesenchymal stem cells to vascular cells regulated by the HMGB1/RAGE axis: its application in cell therapy for transplant arteriosclerosis

Meng

Chen

et al. 2018

Stem Cell Res Ther

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“…Within 6 months, however, vasospasm, thrombosis, and intimal hyperplasia significantly induce restenosis of the arterial blood vessels in 15–40% of treated patients [ 3 , 7 ]. The pathogenesis of intimal hyperplasia after vascular injury is believed to be a serious problem for long-term and adequate blood supply by arterial blood vessels [ 8 , 9 ]. Thus, researchers are currently focusing on prevention of the restenosis of the arterial vascular wall.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Salusin-α Inhibits Vascular Intimal Hyperplasia in an Atherosclerotic Rabbit Model

Qian

Sun

et al. 2018

BioMed Research International

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Inhibiting vascular endothelial foam is the focus of clinical attention. Using SonoVue (an ultrasound contrast agent), the salusin-α gene was transfected into the arterial intima of an atherosclerotic rabbit model induced by a high-fat diet in this study. Subsequently the model of blood lipid indexes, the pathological structure of the intima, and changes in molecules regulating atherosclerosis were investigated. The high-density lipoprotein C and apolipoprotein A values in the salusin-α gene overexpression (P) group were higher than those in the salusin-α gene interference (RP) group (P < 0.05), whereas the total cholesterol, low-density lipoprotein C, and apolipoprotein B values were reversed. Rabbits in the P group showed significantly thinner vascular intimal thickness than that of other experimental groups (P < 0.05). The expression of positive regulators of atherosclerosis (ABCA1, ABCG1) was higher in the P group than that in the RP group (P < 0.05), and the opposite effect was observed for negative regulators (ACAT1, CD36). Thus, our results showed that the overexpression of salusin-α gene inhibited the proliferation of the vascular intima, thereby throwing some light on understanding the mechanism how salusin-α gene expression interfered with the foaming of vascular intimal cells.

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“…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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Endothelial-like cells differentiated from mesenchymal stem cells attenuate neointimal hyperplasia after vascular injury

Cited by 13 publications

References 25 publications

The differentiation of mesenchymal stem cells to vascular cells regulated by the HMGB1/RAGE axis: its application in cell therapy for transplant arteriosclerosis

The differentiation of mesenchymal stem cells to vascular cells regulated by the HMGB1/RAGE axis: its application in cell therapy for transplant arteriosclerosis

Overexpression of Salusin-α Inhibits Vascular Intimal Hyperplasia in an Atherosclerotic Rabbit Model

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

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