Abstract 3899: SDF-1α Mediates the Therapeutic Effect of Human Adipose-Derived Stem Cells on Acute Myocardial Infarction Recruiting Bone Marrow-Derived Endothelial Progenitor Cells

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Masaaki Ii ◽  
Ayumi Yokoyama ◽  
Miki Horii ◽  
Hiroshi Akimaru ◽  
Takayuki Asahara
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Cardiac Function ◽  
Therapeutic Effect ◽  
Heart Diseases ◽  
Capillary Density ◽  
Ischemic Myocardium ◽  
Control Group ◽  
Adipose Derived Stem Cells ◽  
Ischemic Heart Diseases

Background: Recently, human multipotent adipose-derived stem cells (hMADSs) have been isolated featuring extensive expansion capacity ex vivo. However, little is known about the therapeutic efficacy of hMADS in ischemic heart diseases. We tested the hypothesis that hMADS transplantation may contribute to cardiac functional recovery following myocardial infarction (MI). Methods and Results: Nude rats were either transplanted with hMADSs (5x10 5 /rat, n=10) or PBS (control, n=9) in ischemic myocardium immediately following MI induction. The cardiac function, infarct size and capillary density in the peri-infarct area were evaluated by echocardiography and immunostaining 28 days after surgery. The cardiac function was significantly greater with increased capillary density and reduced fibrosis area in the hMADS group than that in the control group. Next, we examined tissue regeneration in the infarct heart by the transplanted hMADSs. However, remarkable differentiation of hMADSs into any cardiac cell lineages was not detected. To explore another mechanism for the favorable effect of hMADSs, we further examined mRNA expression of cytokines in hMADSs under hypoxic conditions. Although hypoxia decreased the expressions, robust VEGF, bFGF, and SDF-1α expressions were detected in hMADSs. Notably, the stem/progenitor chemokine SDF-1α expression in hMADSs was significantly greater than that in human mesenchymal stem cells that are well known to have a therapeutic effect on ischemic heart diseases. We then focused on SDF-1α /CXCR4 axis and examined the contribution of bone marrow (BM)-derived endothelial progenitor cells (EPCs), that have CXCR4 receptor for SDF-1v, to ischemic myocardium using a Tie2/LacZ BM transplantation nude mouse model. β-gal positive EPCs are frequently observed in ischemic myocardium in the hMADS group compared to the control group. Conclusion: hMADSs exhibit a therapeutic effect on cardiac function following MI with the production of VEGF, bFGF, and SDF-1α demonstrating paracrine effects rather than direct contribution to cardiac regeneration. These findings suggest that transplanted hMADSs and recruited EPCs may synergistically promote angiogenesis playing a role in ischemic myocardium.

scholarly journals Transplantation of autologous adipose-derived stem cells ameliorates cardiac function in rabbits with myocardial infarction

2007 ◽  
Vol 120 (4) ◽  
pp. 300-307 ◽  
Author(s):  
Duan-zhen ZHANG ◽  
Lu-yue GAI ◽  
Hong-wei LIU ◽  
Qin-hua JIN ◽  
Jian-hua HUANG ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Cardiac Function ◽  
Adipose Derived Stem Cells

scholarly journals Dynamic Tracking of Injected Mesenchymal Stem Cells after Myocardial Infarction in Rats: A Serial 7T MRI Study

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xiuyu Chen ◽  
Minjie Lu ◽  
Ning Ma ◽  
Gang Yin ◽  
Chen Cui ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Capillary Density ◽  
Left Ventricular ◽  
Cine Mri ◽  
Control Group

Purpose.To track the fate of micron-sized particles of iron oxide (MPIO) labeled mesenchymal stem cells (MSCs) in vivo in a rat myocardial infarction model using 7T magnetic resonance imaging (MRI) scanner.Materials and Methods.Male MSCs (2 × 106/50 μL) dual-labeled with MPIO and CM-DiI were injected into the infarct periphery 7 days after myocardial infarction (MI). The control group received cell-free media injection. The temporal stem cell location, signal intensity, and cardiac function were dynamically assessed using a 7T MRI at 24 h before transplantation (baseline), 3 days, 2 weeks, and 4 weeks after transplantation, respectively.Results.MR hypointensities caused by MPIOs were observed on T2⁎-weighted images at all time points after MSCs injection. Cine-MRI showed that MSCs moderated progressive left ventricular remodeling. Double staining for iron and CD68 revealed that most of the iron-positive cells were CD68-positive macrophages. Real-time PCR for rat SRY gene showed the number of survival MSCs considerably decreased after transplantation. MSC-treated hearts had significantly increased capillary density in peri-infarct region and lower cardiomyocytes apoptosis and fibrosis formation.Conclusions.Iron particles are not a reliable marker for in vivo tracking the long-term fate of MSCs engraftment. Despite of poor cell retention, MSCs moderate left ventricular remodeling after MI.

Adipose-derived stem cells are an effective cell candidate for treatment of heart failure: an MR imaging study of rat hearts

2009 ◽  
Vol 297 (3) ◽  
pp. H1020-H1031 ◽  
Author(s):  
Lei Wang ◽  
Jixian Deng ◽  
Weichen Tian ◽  
Bo Xiang ◽  
Tonghua Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Cardiac Function ◽  
Recovery Period ◽  
Capillary Density ◽  
Left Ventricular ◽  
Border Zone ◽  
Wall Thickening ◽  
Adipose Derived Stem Cells ◽  
Rat Hearts

This study assessed the potential therapeutic efficacy of adipose-derived stem cells (ASCs) on infarcted hearts. Myocardial infarction was induced in rat hearts by occlusion of the left anterior descending artery (LAD). One week after LAD occlusion, the rats were divided into three groups and subjected to transplantation of ASCs or transplantation of cell culture medium (CCM) or remained untreated. During a 1-mo recovery period, magnetic resonance imaging showed that the ASC-treated hearts had a significantly greater left ventricular (LV) ejection fraction and LV wall thickening than did the CCM-treated and untreated hearts. The capillary density in infarct border zone was significantly higher in the ASC-treated hearts than in the CCM-treated and untreated hearts. However, only 0.5% of the ASCs recovered from the ASC-treated hearts were stained positive for cardiac-specific fibril proteins. It was also found that ASCs under a normal culture condition secreted three cardiac protective growth factors: vascular endothelial growth factor, hepatocyte growth factor, and insulin-like growth factor-1. Results of this study suggest that ASCs were able to improve cardiac function of infarcted rat hearts. Paracrine effect may be the mechanism underlying the improved cardiac function and increased capillary density.

scholarly journals Melatonin pretreatment can improve the therapeutic effect of Adipose-derived Stem Cells on CCl4-induced liver fibrosis

2021 ◽  
Author(s):  
Ziqiang Zhang ◽  
Yingying Sun ◽  
Haojie Wang ◽  
Yuxiang Yang ◽  
Ruiqi Dong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Fibrosis ◽  
Therapeutic Effect ◽  
Control Group ◽  
Group Model ◽  
Adipose Derived Stem Cells ◽  
Model Group ◽  
Nuclear Fragmentation ◽  
Apoptotic Genes ◽  
And Control

Abstract Background and PurposeIn this study, the therapeutic effect of Mel-incubated ADSCs on CCl4-induced hepatic fibrosis was investigated. MethodsThe experiment was arranged into ADSCS group, ADSCS + Mel group, Model group and Control group with 10 mice in each group. The other three groups of mice were intraperitoneally injected with 8% CCl4, and the control group was injected with the same dose of PBS twice a week for 4 weeks. From the fifth week, ADSCs group and ADSCs + Mel group mice were injected with 1×106 cells/1 ml PBS dose of ADSCs and 50 μM Mel pretreated ADSCs into tail vein, respectively, twice a week for 2 weeks, and mice in the control and model groups were injected with the same dose of PBS. Samples were tested after six weeks. ResultsIn model group, severe histomathological changes were observed in liver, including severe vacuolation, nuclear fragmentation and liver fibrosis, and these changes were ameliorated by Mel pretreated ADSCs. At the same time, RT-qPCR results showed that Mel-induced ADSCs significantly inhibited the expression of pro-apoptotic genes (Caspase-8, Bax and Caspase-3), and promoted the expression of anti-apoptotic gene (Bcl-2). Immunohistochemical results showed that a large number of MMP-9, TGF-β, MMP-2 yellow-stained positive cells were found in the liver tissues of the model group, while the expression of positive cells was blocked by Mel-induced ADSCs. Conclusion and ImplicationsADSCs pretreated with Mel significantly improved CCl4-induced liver fibrosis, which provides a reference for clinical treatment of liver injury with mesenchymal stem cells.

Impact of Bone Marrow Mesenchymal Stem Cells That Express Vascular Endothelial Growth Factor on Cardiac Function After Myocardial Infarction

2021 ◽  
Vol 11 (1) ◽  
pp. 44-50
Author(s):  
Yongming He ◽  
Ping Li ◽  
Yunlong Chen ◽  
Youmei Li
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cardiac Function ◽  
Troponin T ◽  
Gene Transfection ◽  
Control Group ◽  
Marrow Mesenchymal Stem Cells ◽  
The Impact

Transplanted bone marrow mesenchymal stem cells (MSCs) can differentiate into cardiomyocytes and may have the potential to replace necrotic cardiomyocytes resulting from myocardial infarction (MI). Here we established a method for transfection of MSCs with an expression vector encoding human vascular Eedothelial Ggowth Ffctor (hVEGF). We evaluated the impact of transplantation of transfected MSCs on the recovery cardiac function and angiogenesis in a rat model of MI. Rat MSCs were separated by density gradient centrifugation; their specific surface markers were examined as was their ability to differentiate. MSCs were then transfected with pcDNA 3.1-hVEGF 165 or control-containing liposomes. Rats in the experimental MI groups received transfected MSCs, MSCs alone, or gene-transfection alone; controls included a no intervention MI group and a group that was not subjected to ischemia. Among the results, MSCs were successfully isolated and cultured. Among the intervention groups, those that received transplantation of MSCs expressing hVEGF 165 included the smallest areas of infarction and demonstrated the best recovery of cardiac function overall. Moreover, capillary density detected in this group was significantly greater than in the control group and likewise greater than in rats transplanted with MSCs alone. BrdU and Troponin-T staining revealed differential increases in the number of viable cardiomyocytes within the infarction areas; some cardiomyocytes were double-positive. Likewise, evaluation using RT-PCR revealed higher expression levels of hVEGF in rats transplanted with transfected cells compared to those treated with gene transfection alone.

scholarly journals Harnessing the secretome of adipose-derived stem cells in the treatment of ischemic heart diseases

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiaoting Li ◽  
Teng Ma ◽  
Jiacheng Sun ◽  
Mingjing Shen ◽  
Xiang Xue ◽  
...  
Keyword(s):  
Stem Cells ◽  
Heart Diseases ◽  
Ischemic Heart ◽  
Adipose Derived Stem Cells ◽  
Ischemic Heart Diseases

Abstract 1841: Stromal Cell Derived Factor-1 Increases Capillary Density But Does Not Contribute To Cardiomyocyte Replacement After Experimental Myocardial Infarction

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Francesco Loffredo ◽  
Vincent F Segers ◽  
Catherine MacGillivray ◽  
Richard T Lee
Keyword(s):  
Myocardial Infarction ◽  
Stem Cell ◽  
Cardiac Function ◽  
Stromal Cell ◽  
High Efficiency ◽  
Capillary Density ◽  
Control Group ◽  
Fate Mapping ◽  
Remote Areas ◽  
Stromal Cell Derived Factor

Background. The mechanisms by which regenerative therapies improve cardiac function are incompletely defined. Numerous laboratories have demonstrated that the stem cell chemoattractant Stromal cell derived factor-1 (SDF-1) improves cardiac function after myocardial infarction (MI). This study used a genetic fate-mapping approach to ask the question: Is the beneficial effect of SDF-1 delivery due to cardiomyocyte regeneration, increased capillary density, or both? Methods. We used a genetic fate-mapping system that allows “pulse-chase” studies of cardiomyocyte turnover in mice. We crossed an inducible cardiomyocyte-specific Mer-Cre-Mer transgenic mouse with Z/EG reporter mice. Using a high-efficiency 4-OH-tamoxifen protocol, we then induced Cre recombination and expression of GFP in cardiomyocytes only. SDF-1(S4V), a protease-resistant form of SDF-1, was delivered with nanofibers after coronary ligation. Results. The percentage of pulse-labeled GFP+ cardiomyocytes was 81±4% (n=6) in sham-operated mice, as anticipated with this system. GFP+ cardiomyocytes were 60±5% and 69±4% (n=11) respectively at MI border and MI remote areas of the control nanofiber group, consistent with our previous study and suggesting a significant stem/precursor cell contribution to cardiomyocyte replacement after injury (P<0.0001). GFP+ cardiomyocytes were 65±9% and 76±6% (n=10) respectively at MI border and MI remote areas of the SDF-1(S4V)-RAD group (p=ns vs nanofiber control group), indicating no significantly increase in cardiomyocyte refreshment attributable to SDF-1. However, capillary density increased from 204.7 ± 10.1/mm2 in the nanofiber control group to 308.9 ± 21.9/mm2 in SDF-1(S4V)-RAD + nanofiber group (p =0.0003). Conclusion. Using genetic “pulse-chase” fate mapping, these data indicate that the stem cell chemoattractant SDF-1 does not induce measurable adult mammalian cardiomyocyte replacement by stem/precursor cells following injury. However, SDF-1 significantly increases myocardial capillary density, suggesting that increased angiogenesis but not cardiogenesis is responsible for the beneficial effects of SDF-1 on cardiac function.

Adrenomedullin enhances therapeutic potency of bone marrow transplantation for myocardial infarction in rats

2005 ◽  
Vol 288 (3) ◽  
pp. H1444-H1450 ◽  
Author(s):  
Takafumi Fujii ◽  
Noritoshi Nagaya ◽  
Takashi Iwase ◽  
Shinsuke Murakami ◽  
Yoshinori Miyahara ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Bone Marrow ◽  
Infarct Size ◽  
Subcutaneous Administration ◽  
Capillary Density ◽  
Left Ventricular ◽  
Ischemic Myocardium ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Saline Control ◽  
Control Group

Adrenomedullin (AM), a potent vasodilator, induces angiogenesis and inhibits cell apoptosis through the phosphatidylinositol 3-kinase/Akt pathway. Transplantation of bone marrow-derived mononuclear cells (MNC) induces angiogenesis. We investigated whether infusion of AM enhances the therapeutic potency of MNC transplantation in a rat model of myocardial infarction. Immediately after coronary ligation, bone marrow-derived MNC (5 × 106 cells) were injected into the ischemic myocardium, followed by subcutaneous administration of 0.05 μg·kg−1·min−1 AM (AM-MNC group) or saline (MNC group) for 3 days. Another two groups of rats received subcutaneous administration of AM alone (AM group) or saline (control group). Hemodynamic and histological analyses were performed 4 wk after treatment. Cardiac infarct size was significantly smaller in the MNC and AM groups than in the control group. A combination of AM infusion and MNC transplantation demonstrated a further decrease in infarct size. Left ventricular (LV) maximum change in pressure over time and LV fractional shortening were significantly improved only in the AM-MNC group. AM significantly increased capillary density in ischemic myocardium, suggesting the angiogenic potency of AM. AM infusion plus MNC transplantation demonstrated a further increase in capillary density compared with AM or MNC alone. Although MNC apoptosis was frequently observed 72 h after transplantation, AM markedly decreased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells among the transplanted MNC. In conclusion, AM enhanced the angiogenic potency of MNC transplantation and improved cardiac function in rats with myocardial infarction. This beneficial effect may be mediated partly by the angiogenic property of AM itself and by its antiapoptotic effect on MNC.

P5397Mesenchymal stem cells derived from bone marrow promotes cardiomyocytes survival under hypoxia through exosomal miR-210

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Cheng ◽  
X Y Song ◽  
L Chen ◽  
R D Xu ◽  
Q Qin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Cardiac Function ◽  
Conditioned Medium ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Ventricular Ejection Fraction ◽  
Paracrine Effect

Abstract Mesenchymal stem cells derived from bone marrow promotes cardiomyocytes survival under hypoxia through exosomal miR-210 Background A paracrine effect was regarded as the key mechanism involved in the MSC (mesenchymal stem cell)-based treatment for myocardial infarction. In our pilot experiments, hypoxia remarkably promotes MSC to paracrine exosomal miR-210, which could significantly enhance the cardiomyocytes survival in hypoxic incubation, suggesting that exosomal miR-210 played critical roles in the favorable paracrine effect of MSC on cardiomyocytes. Purpose The aim of this study was to investigate the important mechanism by which MSCs promote the tolerance of cardiomyocytes to hypoxia by secreting exosomal miR-210. Methods and results The exosomes were isolated from MSCs conditioned medium through ultracentrifugation, and we detected that miR-210 was the most abundant in MSC-exosome and increased most prominently in the hypoxia. The extracted exosomes were prepared for conditioned medium and the effect on myocardial protection was examined. The viability of control group was much better than the cardiomyocytes treated with hypoxia, but it was further increased in the presence of MSC-exosome, however, measurement was significantly lower in cardiomyocytes in hypoxia with exosomes derived from MSCs treated with GW4869. Subsequently, the co-localization of miR-210 with exosome-specific surface markers CD81 and CD63 were observed by immunofluorescence technique. Continuous magnetic live cell imaging was used to observe the uptake of exosome by cardiomyocytes, and fluorescence localization was used to observe the localization of miR-210 with Cy3 fluorescence in cardiomyocytes. Then, we demonstrated that MSCs exosomal miR-210 exerts the cardioprotective effect by regulating the AIFM3 (apoptosis-inducing factor mitochondria-associated protein 3), and we directly overexpressed miRNA-210 in cardiomyocytes and the results showed that the regulatory activity of the intake of exosomal miR-210 was consistent with that of the biological exosomal miR-210. Finally, we verified the protective effect on the ischemic myocardium by constructing rat myocardial infarction models. The level of apoptosis was detected at 1 week after myocardial infarction. The left ventricular ejection fraction and ventricular remodeling were measured at 4 weeks. In vivo, we demonstrated that explanted miR-210 from transplanted MSCs significantly reduced myocardial necrosis and apoptosis induced by ischemia and improved cardiac function and myocardial remodeling. Conclusion Here, we show that the exosomal miR-210 secreted by MSCs significantly increase the viability of cardiomyocytes and cardiac function. These findings suggest that exosomal miR-210 is a key effector that mediates the protection against hypoxia. Acknowledgement/Funding National Natural Science Foundation of China (Grant Nos. 81470467)

Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis

2004 ◽  
Vol 287 (6) ◽  
pp. H2670-H2676 ◽  
Author(s):  
Noritoshi Nagaya ◽  
Takafumi Fujii ◽  
Takashi Iwase ◽  
Hajime Ohgushi ◽  
Takefumi Itoh ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiac Function ◽  
Intravenous Administration ◽  
Diastolic Pressure ◽  
Troponin T ◽  
Left Ventricular ◽  
Control Group

Mesenchymal stem cells (MSCs) are pluripotent cells that differentiate into a variety of cells, including cardiomyocytes and endothelial cells. However, little information is available regarding the therapeutic potency of systemically delivered MSCs for myocardial infarction. Accordingly, we investigated whether intravenously transplanted MSCs induce angiogenesis and myogenesis and improve cardiac function in rats with acute myocardial infarction. MSCs were isolated from bone marrow aspirates of isogenic adult rats and expanded ex vivo. At 3 h after coronary ligation, 5 × 106 MSCs (MSC group, n = 12) or vehicle (control group, n = 12) was intravenously administered to Lewis rats. Transplanted MSCs were preferentially attracted to the infarcted, but not the noninfarcted, myocardium. The engrafted MSCs were positive for cardiac markers: desmin, cardiac troponin T, and connexin43. On the other hand, some of the transplanted MSCs were positive for von Willebrand factor and formed vascular structures. Capillary density was markedly increased after MSC transplantation. Cardiac infarct size was significantly smaller in the MSC than in the control group (24 ± 2 vs. 33 ± 2%, P < 0.05). MSC transplantation decreased left ventricular end-diastolic pressure and increased left ventricular maximum dP/d t (both P < 0.05 vs. control). These results suggest that intravenous administration of MSCs improves cardiac function after acute myocardial infarction through enhancement of angiogenesis and myogenesis in the ischemic myocardium.

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