OVER-EXPRESSION OF SDF1α ENHANCES CARDIAC REPAIR BY CARDIAC STEM CELLS

2014 ◽  
Vol 30 (10) ◽  
pp. S185
Author(s):  
E.L. Tilokee ◽  
R. Jackson ◽  
A. Mayfield ◽  
N. Latham ◽  
B. Ye ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cardiac Repair ◽  
Cardiac Stem Cells ◽  
Over Expression

Abstract 15747: Over-Expression of Insulin-Like Growth Factor-1 by Human Cardiac Stem Cells Enhances Long-Term Retention of Transplanted Cells While Promoting Salvage of Injured Myocardium

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Robyn Jackson ◽  
Everad L Tilokee ◽  
Nicholas Latham ◽  
Bin Ye ◽  
Munir Boodhwani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Annexin V ◽  
Cardiac Repair ◽  
Population Doubling ◽  
Cardiac Stem Cells ◽  
Insulin Like Growth Factor ◽  
Over Expression ◽  
Myocardial Apoptosis

Background: Insulin-like growth factor (IGF-1) is a potent pro-survival cytokine that is not robustly expressed by human cardiac stem cells (CSCs). Previously, we have shown that paracrine engineering of CSCs with IGF-1 improves cell-mediated cardiac repair. Here, we explore the mechanisms underlying IGF-1 enhanced cardiac repair by CSCs. Methods/Results: Sub-culture of isolated c-Kit+, CD90+ and lineage negative cells (c-Kit-/CD90-) demonstrated that the natural low level production of IGF-1 by CSCs (149±16 pg/ml*mg) is secreted by all 3 sub-populations. After culture in hypoxic reduced serum media, lentiviral mediated over-expression of IGF-1 enhanced proliferation (population doubling time: 1.4±1.7 vs.-0.9±1.2 and -1.9±2.4 days, respectively; p≤0.01), expression of pro-survival transcripts (AKT, ERK and MAPK pathways) and pro-survival proteins (Bcl-2, Bcl-x, HIF-1a; p≤0.01) while decreasing expression of apoptotic markers (3.5±0.9 and 3.7±0.9 fold less annexin V; p≤0.01) as compared to GFP- and non-transduced CSCs. The high expression of the IGF-1 (79±3%) or the insulin receptor (61±5%) on CSCs suggests that autocrine pro-survival pre-conditioning underlies these effects. Direct and indirect co-culture of CSCs with neonatal rat ventricular cardiomyocytes (NRVMs) within hypoxic conditions demonstrated that IGF-1 promoted indirect myocardial repair by increasing NRVM viability and pro-survival signaling (Bcl2+; p≤0.01) while reducing apoptosis (annexin V+; p≤0.05) as compared GFP- or non-transduced CSCs. Transplant of CSCs genetically engineered to over-express IGF-1 into immunodeficient mice one week after infarction boosted IGF-1 content within infarcted tissue by 2.9±0.2 fold (p=0.004) and long-term engraftment (+4 weeks human alu content increased by 9.1±4 fold; p=0.05) while reducing myocardial apoptosis (3.4±0.3 and 2.5±0.5 fold reduction expression of Bax and p53, respectively; p<0.05) and long-term myocardial scarring (+ 4 weeks 2.2±0.4 fold less; p=0.01) as compared to GFP-transduced CSCs. Conclusions: Transplantation of IGF-1 enriched CSCs enhances cardiac repair by boosting transplant cell survival and reducing myocardial apoptosis to improve myocardial function and salvage of damaged myocardium.

scholarly journals Local activation of cardiac stem cells for post-myocardial infarction cardiac repair

2012 ◽  
Vol 16 (11) ◽  
pp. 2549-2563 ◽  
Author(s):  
Zhuzhi Wen ◽  
Zun Mai ◽  
Haifeng Zhang ◽  
Yangxin Chen ◽  
Dengfeng Geng ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Cardiac Repair ◽  
Post Myocardial Infarction ◽  
Cardiac Stem Cells ◽  
Local Activation

scholarly journals INCREASED POTENCY OF CARDIAC STEM CELLS COMPARED TO BONE MARROW MESENCHYMAL STEM CELLS IN CARDIAC REPAIR

2011 ◽  
Vol 57 (14) ◽  
pp. E1014
Author(s):  
Behzad Nasehi Oskouei ◽  
Guillaume Lamirault ◽  
Chacko Joseph ◽  
Stephanie Landa ◽  
Marc Dauer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cardiac Repair ◽  
Cardiac Stem Cells ◽  
Marrow Mesenchymal Stem Cells

scholarly journals Another angiogenesis-independent role for VEGF: SDF1-dependent cardiac repair via cardiac stem cells

2011 ◽  
Vol 91 (3) ◽  
pp. 369-370 ◽  
Author(s):  
F. Claes ◽  
W. Vandevelde ◽  
L. Moons ◽  
M. Tjwa
Keyword(s):  
Stem Cells ◽  
Cardiac Repair ◽  
Cardiac Stem Cells

Mesenchymal Stem Cells with eNOS Over-Expression Enhance Cardiac Repair in Rats with Myocardial Infarction

2016 ◽  
Vol 31 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Leilei Chen ◽  
Yuan Zhang ◽  
Liangliang Tao ◽  
Zhijian Yang ◽  
Liansheng Wang
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiac Repair ◽  
Over Expression

scholarly journals Human Blood and Cardiac Stem Cells Synergize to Enhance Cardiac Repair When Cotransplanted Into Ischemic Myocardium

Circulation ◽  
2013 ◽  
Vol 128 (11_suppl_1) ◽  
pp. S105-S112 ◽  
Author(s):  
N. Latham ◽  
B. Ye ◽  
R. Jackson ◽  
B.-K. Lam ◽  
D. Kuraitis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Human Blood ◽  
Cardiac Repair ◽  
Ischemic Myocardium ◽  
Cardiac Stem Cells

scholarly journals Hepatocyte growth factor/Met gene transfer in cardiac stem cells—potential for cardiac repair

2010 ◽  
Vol 105 (4) ◽  
pp. 443-452 ◽  
Author(s):  
Rosalinda Madonna ◽  
Gregg Rokosh ◽  
Raffaele Caterina ◽  
Roberto Bolli
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Gene Transfer ◽  
Hepatocyte Growth Factor ◽  
Cardiac Repair ◽  
Cardiac Stem Cells ◽  
Hepatocyte Growth
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