scholarly journals Statin Administration Does Not Improve the Mobilization of Very Small Embryonic-Like Stem Cells (VSELs) in Contrast to Resveratrol Treatment in a Murine Model of Acute Myocardial Infarction

2012 ◽  
pp. 543-549 ◽  
Author(s):  
H. WANG ◽  
Y.-J. YANG ◽  
H.-Y. QIAN ◽  
Q. ZHANG ◽  
L.-J. GAO ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cell ◽  
Cardiac Function ◽  
Stromal Cell ◽  
Statin Treatment ◽  
Positive Control ◽  
Short Term ◽  
Cellular Cardiomyoplasty ◽  
Stromal Cell Derived Factor

We have found that short-term statin treatment plus stem cell transplantation in acutely infarcted hearts improves cardiac function because statins promote the efficacy of cellular cardiomyoplasty. Autologous Sca-1+Lin-CD45-(CXCR+) very small embryonic-like stem cell (VSEL) mobilization in acute myocardial infarction (AMI) correlates with the preservation of cardiac function. Whether short-term atorvastatin (Ator) can enhance the mobilization or recruitment of VSELs in AMI is still unclear. We divided mice into 4 groups: 1) sham; 2) AMI; 3) AMI+resveratrol (RSV) as a positive control; and 4) AMI+Ator. There was an increase in the circulating VSEL/full population of leukocytes (FPL) ratio 48 hours after AMI, and AMI+RSV increased it further. Ator administration did not increase the VSEL/FPL ratio. The cardiac stromal cell-derived factor-1 (SDF-1) and SDF-1α levels were in agreement with the results of VSEL mobilization. One week after AMI, more Sca-1+CXCR+ cells were recruited to the myocardium of AMI+RSV mice but not AMI+Ator mice. Short-term Ator administration failed to upregulate cardiac SDF-1 and could not enhance the recruitment of VSELs early after AMI.

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.

scholarly journals Preclinical Evaluation of the Engineered Stem Cell Chemokine Stromal Cell–Derived Factor 1α Analog in a Translational Ovine Myocardial Infarction Model

2014 ◽  
Vol 114 (4) ◽  
pp. 650-659 ◽  
Author(s):  
John W. MacArthur ◽  
Jeffrey E. Cohen ◽  
Jeremy R. McGarvey ◽  
Yasuhiro Shudo ◽  
Jay B. Patel ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cell ◽  
Stromal Cell ◽  
Preclinical Evaluation ◽  
Stromal Cell Derived Factor

scholarly journals Combinatorial treatment of acute myocardial infarction using stem cells and their derived exosomes resulted in improved heart performance

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Peisen Huang ◽  
Li Wang ◽  
Qing Li ◽  
Jun Xu ◽  
Junyan Xu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Stem Cell ◽  
Cardiac Function ◽  
Inflammatory Responses ◽  
Heart Function ◽  
Border Zone ◽  
Inflammatory Factor ◽  
Intramyocardial Injection

Abstract Background Bone marrow mesenchymal stem cells (MSCs) are among the most common cell types to be used and studied for cardiac regeneration. Low survival rate and difficult retention of delivered MSCs in infarcted heart remain as major challenges in the field. Co-delivery of stem cell-derived exosomes (Exo) is expected to improve the recruitment and survival of transplanted MSCs. Methods Exo was isolated from MSCs and delivered to an acute myocardial infarction (AMI) rat heart through intramyocardial injection with or without intravenous infusion of atrovastatin-pretreated MSCs on day 1, day 3, or day 7 after infarction. Echocardiography was performed to evaluate cardiac function. Histological analysis and ELISA test were performed to assess angiogenesis, SDF-1, and inflammatory factor expression in the infarct border zone. The anti-apoptosis effect of Exo on MSCs was evaluated using flow cytometry and Hoechst 33342 staining assay. Results We found that intramyocardial delivery of Exo followed by MSC transplantation (in brief, Exo+MSC treatment) into MI hearts further improved cardiac function, reduced infarct size, and increased neovascularization when compared to controls treated with Exo or MSCs alone. Of note, comparing the three co-transplanting groups, intramyocardially injecting Exo 30 min after AMI combined with MSCs transplantation at day 3 after AMI achieved the highest improvement in heart function. The observed enhanced heart function is likely due to an improved microenvironment via Exo injection, which is exemplified as reduced inflammatory responses and better MSC recruitment and retention. Furthermore, we demonstrated that pre-transplantation injection of Exo enhanced survival of MSCs and reduced their apoptosis both in vitro and in vivo. Conclusions Combinatorial delivery of exosomes and stem cells in a sequential manner effectively reduces scar size and restores heart function after AMI. This approach may represent as an alternative promising strategy for stem cell-based heart repair and therapy.

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