Cardiac Stem Cells Cultured From Aged Donors With Ischemic Cardiomyopathy Have an Impaired Regenerative Capacity Due to Altered Responses to Oxidative Stress

2013 ◽  
Vol 29 (10) ◽  
pp. S236
Author(s):  
G. Rafatian ◽  
M. Kamkar ◽  
E. Tilokee ◽  
N. Latham ◽  
C.V. Cheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Ischemic Cardiomyopathy ◽  
Cardiac Stem Cells ◽  
Regenerative Capacity ◽  
Cells Cultured

scholarly journals 3D-model of adult cardiac stem cells promotes cardiac differentiation and resistance to oxidative stress

2008 ◽  
Vol 105 (2) ◽  
pp. 612-623 ◽  
Author(s):  
T.J. Bartosh ◽  
Zhaohui Wang ◽  
Armando A. Rosales ◽  
S. Dan Dimitrijevich ◽  
Rouel S. Roque
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
3D Model ◽  
Cardiac Differentiation ◽  
Cardiac Stem Cells

The Regenerative Capacity of Cardiac Stem Cells Inversely Correlates With Risk Factors for Coronary Artery Disease

2013 ◽  
Vol 29 (10) ◽  
pp. S347
Author(s):  
M. Fitzpatrick ◽  
N. Latham ◽  
E.L. Tilokee ◽  
G.A. Wells ◽  
K. Lam ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Stem Cells ◽  
Coronary Artery ◽  
Cardiac Stem Cells ◽  
Regenerative Capacity ◽  
Artery Disease

Abstract 52: Impaired Ephrin A1/EphA2 Signaling Results in Defective Migration and Homing of Senescent Human Cardiac Stem Cells

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Ramaswamy Kannappan ◽  
Yingnan Bai ◽  
Sergio Signore ◽  
Maria Cimini ◽  
Joao Ferreira-Martins ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Fold Increase ◽  
Cardiac Stem Cells ◽  
Ventricular Performance ◽  
Post Translational Modifications ◽  
Caveolin 1 ◽  
Molecular Alterations ◽  
Injured Area ◽  
Pre Treatment

Aging is the major independent risk factor for chronic heart failure. Despite the presence of cardiac stem cells (CSCs), the old human heart undergoes progressive deterioration in ventricular performance, coupled with scattered foci of fibrosis and accumulation of poorly contracting myocytes. We raised the possibility that defects in the translocation of senescent human CSCs (hCSCs) to the sites of damage constitute a key determinant in the manifestation of the aging myopathy. We report that ephrin A1-EphA2 receptor signaling is a critical modulator of hCSC motility. Ephrin A1, a membrane-anchored protein, is expressed on the myocyte sarcolemma and acts as a ligand for the EphA2 receptor on neighboring hCSCs, facilitating their migration. Pre-treatment of young hCSCs with ephrin A1 resulted in enhanced movement of the transplanted cells to the necrotic tissue, with formation of new myocardium and improvement in cardiac function. Whether senescent hCSCs promote a comparable regenerative response remained to be established. Surprisingly, the expression of EphA2 did not differ in young and old hCSCs. With respect to young cells, senescent hCSCs showed a 2-fold increase in intracellular ROS levels. Oxidative stress led to post-translational modifications and functional alterations of the EphA2 receptor. Specifically, the ability of ephrin A1 to induce phosphorylation of the EphA2 receptor was markedly attenuated in senescent hCSCs, resulting in inadequate activation of Src family proteins. As a consequence, the phosphorylation and activity of caveolin-1, a substrate of Src kinases, was reduced. These molecular alterations led to impaired endocytosis of the ligand-receptor complex, a cellular process essential for ephrin A1-EphA2 signaling. Lack of endocytosis precluded rearrangement of the actin cytoskeleton and cell migration. Importantly, ephrin A1-stimulated senescent hCSCs delivered to infarcted rats accumulated in proximity of the site of injection and did not translocate to the ischemic area. Thus, oxidative stress interferes with EphA2 signaling in aging hCSCs, negatively affecting their migration. Restoration of the EphA2 function in old hCSCs may enhance their mobilization and improve cell targeting to the injured area.

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

scholarly journals Exosomes Derived from miR-214-Enriched Bone Marrow-Derived Mesenchymal Stem Cells Regulate Oxidative Damage in Cardiac Stem Cells by Targeting CaMKII

2018 ◽  
Vol 2018 ◽  
pp. 1-21 ◽  
Author(s):  
Yan Wang ◽  
Ranzun Zhao ◽  
Debin Liu ◽  
Wenwen Deng ◽  
Guanxue Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Oxidative Damage ◽  
Bioactive Molecules ◽  
Cardiac Stem Cells ◽  
Stress Injury ◽  
Hypoxic Conditions ◽  
Oxidative Stress Injury

Cardiac stem cells (CSCs) have emerged as one of the most promising stem cells for cardiac protection. Recently, exosomes from bone marrow-derived mesenchymal stem cells (BMSCs) have been found to facilitate cell proliferation and survival by transporting various bioactive molecules, including microRNAs (miRs). In this study, we found that BMSC-derived exosomes (BMSC-exos) significantly decreased apoptosis rates and reactive oxygen species (ROS) production in CSCs after oxidative stress injury. Moreover, a stronger effect was induced by exosomes collected from BMSCs cultured under hypoxic conditions (Hypoxic-exos) than those collected from BMSCs cultured under normal conditions (Nor-exos). We also observed greater miR-214 enrichment in Hypoxic-exos than in Nor-exos. In addition, a miR-214 inhibitor or mimics added to modulate miR-214 levels in BMSC-exos revealed that exosomes from miR-214-depleted BMSCs partially reversed the effects of hypoxia-induced exosomes on oxidative damage in CSCs. These data further confirmed that miR-214 is the main effector molecule in BMSC-exos that protects CSCs from oxidative damage. miR-214 mimic and inhibitor transfection assays verified that CaMKII is a target gene of miR-214 in CSCs, with exosome-pretreated CSCs exhibiting increased miR-214 levels but decreased CaMKII levels. Therefore, the miR-214/CaMKII axis regulates oxidative stress-related injury in CSCs, such as apoptosis, calcium homeostasis disequilibrium, and excessive ROS accumulation. Collectively, these findings suggest that BMSCs release miR-214-containing exosomes to suppress oxidative stress injury in CSCs through CaMKII silencing.

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