scholarly journals OVER-EXPRESSION OF MYBL2 REJUVENATES EXPLANT DERIVED CARDIAC STEM CELLS FROM AGED DONORS WITH ISCHEMIC CARDIOMYOPATHY

2017 ◽  
Vol 33 (10) ◽  
pp. S18-S19
Author(s):  
G. Rafatian ◽  
E. Suuronen ◽  
D. Davis
Keyword(s):  
Stem Cells ◽  
Ischemic Cardiomyopathy ◽  
Cardiac Stem Cells ◽  
Over Expression

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 Intracoronary Delivery of Autologous Cardiac Stem Cells Improves Cardiac Function in a Porcine Model of Chronic Ischemic Cardiomyopathy

Circulation ◽  
2013 ◽  
Vol 128 (2) ◽  
pp. 122-131 ◽  
Author(s):  
Roberto Bolli ◽  
Xian-Liang Tang ◽  
Santosh K. Sanganalmath ◽  
Ornella Rimoldi ◽  
Federico Mosna ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cardiac Function ◽  
Ischemic Cardiomyopathy ◽  
Porcine Model ◽  
Cardiac Stem Cells

Cardiac Stem Cells in Patients with Ischemic Cardiomyopathy: Discovery, Translation, and Clinical Investigation

2012 ◽  
Vol 14 (5) ◽  
pp. 491-503 ◽  
Author(s):  
John H. Loughran ◽  
Julius B. Elmore ◽  
Momina Waqar ◽  
Atul R. Chugh ◽  
Roberto Bolli
Keyword(s):  
Stem Cells ◽  
Ischemic Cardiomyopathy ◽  
Clinical Investigation ◽  
Cardiac Stem Cells
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