Marrow-derived MSCs and atorvastatin improve cardiac function in rat model of AMI

Wang, Ailing; Shen, Fengqiang; Liang, Youfeng; Wang, Jing

doi:10.1016/j.ijcard.2010.02.023

Cited by 14 publications

(12 citation statements)

References 15 publications

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“…At 90% confluence, the cells were trypsinized (0.25% trypsin) and passaged at 1:3 ratios. Cells were identified by flow cytometry as described previously (23). MSCs between passages three and four were used for the following experiments.…”

Section: Methodsmentioning

confidence: 99%

Co-treating mesenchymal stem cells with IL-1β and TNF-α increases VCAM-1 expression and improves post-ischemic myocardial function

Wang

Guo

Xie

et al. 2014

Molecular Medicine Reports

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Inflammatory mediators are released by the myocardium following myocardial ischemia as a response to tissue injury, and contribute to cardiac repair and adaptive responses. Treating mesenchymal stem cells (MSCs) with various inflammatory factors activates a series of biological processes that enhance cell-mediated cardioprotection following myocardial infarction (MI). The present study was designed to examine the effect of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) treatment on vascular cell adhesion molecule-1 (VCAM-1) expression in MSCs, and to identify whether cytokine-treated MSCs improve post-ischemic myocardial function in a rat model. MSCs were stimulated with IL-1β and/or TNF-α for 24 h, the production of vascular cell adhesion molecule-1 (VCAM-1) and the adhesion ability of MSCs were assessed by flow cytometry, adhesion assays, quantitative polymerase chain reaction and western blot analysis. The cardiac function was examined by two-dimensional echocardiography. The results demonstrated that in treated MSCs, the secretion of VCAM-1 and the cell adhesion ability were significantly increased, thus markedly improving cardiac function compared with that of the control group (P<0.01). Of all the groups, the rats stimulated with a combination of IL-1β and TNF-α exhibited the greatest cardiac improvements. However, there was no significant difference between the 10 and 20 ng/ml groups which were stimulated with one of the cytokines alone (P>0.05). In conclusion, stimulating MSCs with IL-1β and TNF-α promoted the expression of VCAM-1 and improved post-ischemic cardiac function recovery. Treating MSCs with two cytokines in combination may be a useful method to maximize the potential of cell-based therapy for MI.

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Section: Methodsmentioning

confidence: 99%

Co-treating mesenchymal stem cells with IL-1β and TNF-α increases VCAM-1 expression and improves post-ischemic myocardial function

Wang

Guo

Xie

et al. 2014

Molecular Medicine Reports

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“…Cell culture and the model of hypoxia and SD. The MSCs were isolated from Sprague-Dawley rats (~4 weeks old, weight 80 g) obtained from the Laboratory Animal Center of Anhui Medical University (Hefei, Anhui, China) as previously described (20).…”

Section: Inhibition Of the Endogenous Cse/h 2 S System Contributes Tomentioning

confidence: 99%

“…The adherent, spindle-shaped MSCs were expanded and cultured for no more than two or three passages. Then they were analyzed by flow cytometry for the expression of surface markers as described previously (20). Apoptosis was induced by hypoxia/SD.…”

Section: Inhibition Of the Endogenous Cse/h 2 S System Contributes Tomentioning

confidence: 99%

Inhibition of the endogenous CSE/H2S system contributes to hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells

Guo

et al. 2014

Molecular Medicine Reports

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Mesenchymal stem cells (MSCs) have great potential for repair following acute myocardial infarction. However, a major challenge to MSC therapy is that transplanted cells undergo apoptosis. Hydrogen sulfide (H2S) has recently been proposed as an endogenous mediator of cell apoptosis in various systems. The aim of the present study was to investigate the role of endogenous H2S in hypoxia and serum deprivation (hypoxia/SD)-induced apoptosis in MSCs. The present study demonstrated that exposure of MSCs to hypoxia/SD caused a significant decrease in H2S generation and resulted in marked cell apoptosis. Furthermore, under basal conditions, MSCs expressed cystathionine γ-lyase (CSE) and synthesized H2S, whereas CSE expression and activity was inhibited by hypoxia/SD treatment. Overexpression of CSE not only markedly prevented hypoxia/SD-induced decreases in endogenous H2S generation but also protected MSCs from apoptosis, while inhibition of CSE by its potent inhibitors significantly deteriorated the effect of hypoxia/SD in MSCs. These data indicate that the H2S generation pathway exists in MSCs and the inhibition of the endogenous CSE/H2S system contributes to hypoxia/SD-induced apoptosis in MSCs. Our findings suggest that modulation of the CSE/H2S system is a potential therapeutic avenue for promoting the viability of transplanted MSCs.

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“…Existing evidence suggests that ischemia and hypoxia, inflammation, apoptosis, oxidative stress, and neuroendocrine activation together create a grim and adverse microenvironment in the infracted myocardium to threaten the survival of implanted stem cells [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27]. Clearly, maximizing the survival rate of transplanted cells is a critical step towards maximizing the potential of stem cell therapy for AMI.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have demonstrated that combined therapy with mesenchymal stem cells (MSCs) and atorvastatin, a blood cholesterol-lowering agent, produces synergistic beneficial effects in the treatment of AMI, despite that neither atorvastatin nor MSCs can individually improve ventricular function significantly [15,16,17,18,19,20,21]. These findings retrieved the declining interest in applying and investigating stem cell therapy of AMI, and stirred up new surges for searching better strategies to boost MSCs therapy: combined MSCs therapy and pharmacotherapy is one of these proof-in-principle approaches.…”

Section: Introductionmentioning

confidence: 99%

Atorvastatin Improves Microenvironment to Enhance the Beneficial Effects of BMSCs Therapy in a Rabbit Model of Acute Myocardial Infarction

Tian

et al. 2013

Cell Physiol Biochem

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Background/Aims: To investigate the beneficial effects of atorvastatin added to the cell therapy with bone marrow-derived mesenchymal stromal cells (BMSCs) in a rabbit model of acute myocardial infarction (AMI). Methods: Rabbits were randomly divided into control group (n=10), bone marrow stem cells transplantation group (n=10), and BMSCs + atorvastatin group (n=10). AMI was established by ligating the left descending coronary artery. The left ventricular (LV) function was evaluated by echocardiography. H&E staining and Masson's Trichrome staining were performed to evaluate inflammatory cell infiltration and cardiac fibrosis. Immunohistochemistry and TUNEL were conducted to assess survival, differentiation, and apoptosis of transplanted cells and cardiomyocytes. Results: BMSCs decreased LV systolic and diastolic diameters and increased LV ejection fractions, LV fractional shortening, LV systolic pressure and LV end-diastolic pressure. Atorvastatin synergistically enhanced the BMSCs-induced improvements of ischemic cardiac dysfunction. Atorvastatin reduced inflammatory cell infiltration, cardiac fibrosis, and derangement of myocardial morphology/structure. Atorvastatin added a protective effect to cardiomyocytes against apoptotic cell death in infarct and peri-infarct areas, and also increased the survival rate of implanted BMSCs in acute myocardial ischemia. Atorvastatin also promoted cardiac differentiation of implanted BMSCs in infarct myocardium. Conclusion: Atorvastatin acts to improve the microenvironment both by synergistically enhancing the existing effects of BMSCs and by adding new therapeutic effects to BMSCs transplantation, and this combinational therapy is a superior cell/pharmacological therapeutic approach that merits future preclinical and clinical studies.

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Marrow-derived MSCs and atorvastatin improve cardiac function in rat model of AMI

Cited by 14 publications

References 15 publications

Co-treating mesenchymal stem cells with IL-1β and TNF-α increases VCAM-1 expression and improves post-ischemic myocardial function

Co-treating mesenchymal stem cells with IL-1β and TNF-α increases VCAM-1 expression and improves post-ischemic myocardial function

Inhibition of the endogenous CSE/H2S system contributes to hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells

Atorvastatin Improves Microenvironment to Enhance the Beneficial Effects of BMSCs Therapy in a Rabbit Model of Acute Myocardial Infarction

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