0334: Cellular mechanisms to enhance the regeneration potential of cardiac progenitor cells

In recent years, several studies have investigated cell transplantation as an innovative strategy to restore cardiac function following heart failure. Previous studies have also shown cardiac progenitor cells as suitable candidates for cardiac cell therapy compared with other stem cells. Cellular kit (c-kit) plays an important role in the survival and migration of cardiac progenitor cells. Like other types of cells, in the heart, cellular responses to various stimuli are mediated via coordinated pathways. Activation of c-kit+ cells leads to subsequent activation of several downstream mediators such as PI3K and the MAPK pathways. This review aims to outline current research findings on the role of PI3K/AKT and the MAPK pathways in myocardial regeneration potential of c-kit+.

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Cardiac progenitor cells in terminally failing hearts: Immunohistological observations in human myocardium

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-2007-967414 ◽

2007 ◽

Vol 55 (S 1) ◽

Author(s):

M Arnold ◽

V Kufer ◽

A Schütz ◽

B Reiter ◽

M Fittkau ◽

...

Keyword(s):

Progenitor Cells ◽

Human Myocardium ◽

Cardiac Progenitor Cells

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Breakthrough Regenerative Cardiopoietic Stem Cells and Related Technologies in the Field of Cardiovascular Medicine – From Bench to Bedside

Interventional Cardiology Review ◽

10.15420/icr.2012.7.1.14 ◽

2012 ◽

Vol 7 (1) ◽

pp. 14

Author(s):

Christian Homsy ◽

Keyword(s):

Stem Cells ◽

Cell Therapy ◽

Progenitor Cells ◽

Cardiac Disease ◽

Cardiac Tissue ◽

Cardiac Repair ◽

Cardiac Diseases ◽

Cardiac Progenitor Cells ◽

Biotechnology Company ◽

Cardiovascular Medicine

The scale of cardiac diseases, and in particular heart failure and acute myocardial infarction, emphasises the need for radically new approaches, such as cell therapy, to address the underlying cause of the disease, the loss of functional myocardium. Stem cell-based therapies, whether through transplanted cells or directing innate repair, may provide regenerative approaches to cardiac diseases by halting, or even reversing, the events responsible for progression of organ failure. Cardio3 BioSciences, a leading Belgian biotechnology company focused on the discovery and development of regenerative and protective therapies for the treatment of cardiac disease, was founded in this context in 2004. The company is developing a highly innovative cell therapy approach based on a platform designed to reprogramme the patient’s own stem cells into cardiac progenitor cells. The underlying rationale behind this approach is that, in order to reconstruct cardiac tissue, stem cells need to be specific to cardiac tissue. The key is therefore to provide cardiac-specific progenitor cells to the failing heart to induce cardiac repair.

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Diabetes induces dysregulation of microRNAs associated with survival, proliferation and self-renewal in cardiac progenitor cells

Diabetologia ◽

10.1007/s00125-021-05405-7 ◽

2021 ◽

Author(s):

Nima Purvis ◽

Sweta Kumari ◽

Dhananjie Chandrasekera ◽

Jayanthi Bellae Papannarao ◽

Sophie Gandhi ◽

...

Keyword(s):

Progenitor Cells ◽

Cardiac Progenitor Cells ◽

Self Renewal

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Novel Identified Circular Transcript of RCAN2, circ-RCAN2, Shows Deviated Expression Pattern in Pig Reperfused Infarcted Myocardium and Hypoxic Porcine Cardiac Progenitor Cells In Vitro

International Journal of Molecular Sciences ◽

10.3390/ijms22031390 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1390

Author(s):

Julia Mester-Tonczar ◽

Patrick Einzinger ◽

Johannes Winkler ◽

Nina Kastner ◽

Andreas Spannbauer ◽

...

Keyword(s):

Myocardial Infarction ◽

Progenitor Cells ◽

Regulatory Networks ◽

Circular Rnas ◽

Cardiac Progenitor Cells ◽

Tissue Samples ◽

Healthy Myocardium ◽

Acute Mi

Circular RNAs (circRNAs) are crucial in gene regulatory networks and disease development, yet circRNA expression in myocardial infarction (MI) is poorly understood. Here, we harvested myocardium samples from domestic pigs 3 days after closed-chest reperfused MI or sham surgery. Cardiac circRNAs were identified by RNA-sequencing of rRNA-depleted RNA from infarcted and healthy myocardium tissue samples. Bioinformatics analysis was performed using the CIRIfull and KNIFE algorithms, and circRNAs identified with both algorithms were subjected to differential expression (DE) analysis and validation by qPCR. Circ-RCAN2 and circ-C12orf29 expressions were significantly downregulated in infarcted tissue compared to healthy pig heart. Sanger sequencing was performed to identify the backsplice junctions of circular transcripts. Finally, we compared the expressions of circ-C12orf29 and circ-RCAN2 between porcine cardiac progenitor cells (pCPCs) that were incubated in a hypoxia chamber for different time periods versus normoxic pCPCs. Circ-C12orf29 did not show significant DE in vitro, whereas circ-RCAN2 exhibited significant ischemia-time-dependent upregulation in hypoxic pCPCs. Overall, our results revealed novel cardiac circRNAs with DE patterns in pCPCs, and in infarcted and healthy myocardium. Circ-RCAN2 exhibited differential regulation by myocardial infarction in vivo and by hypoxia in vitro. These results will improve our understanding of circRNA regulation during acute MI.

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Postischemic Revascularization: From Cellular and Molecular Mechanisms to Clinical Applications

Physiological Reviews ◽

10.1152/physrev.00006.2013 ◽

2013 ◽

Vol 93 (4) ◽

pp. 1743-1802 ◽

Cited By ~ 145

Author(s):

Jean-Sébastien Silvestre ◽

David M. Smadja ◽

Bernard I. Lévy

Keyword(s):

Progenitor Cells ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Therapeutic Option ◽

Vascular Wall ◽

Arterial Disease ◽

Cellular Mechanisms ◽

Collateral Growth ◽

Vessel Growth ◽

Ischemic Diseases

After the onset of ischemia, cardiac or skeletal muscle undergoes a continuum of molecular, cellular, and extracellular responses that determine the function and the remodeling of the ischemic tissue. Hypoxia-related pathways, immunoinflammatory balance, circulating or local vascular progenitor cells, as well as changes in hemodynamical forces within vascular wall trigger all the processes regulating vascular homeostasis, including vasculogenesis, angiogenesis, arteriogenesis, and collateral growth, which act in concert to establish a functional vascular network in ischemic zones. In patients with ischemic diseases, most of the cellular (mainly those involving bone marrow-derived cells and local stem/progenitor cells) and molecular mechanisms involved in the activation of vessel growth and vascular remodeling are markedly impaired by the deleterious microenvironment characterized by fibrosis, inflammation, hypoperfusion, and inhibition of endogenous angiogenic and regenerative programs. Furthermore, cardiovascular risk factors, including diabetes, hypercholesterolemia, hypertension, diabetes, and aging, constitute a deleterious macroenvironment that participates to the abrogation of postischemic revascularization and tissue regeneration observed in these patient populations. Thus stimulation of vessel growth and/or remodeling has emerged as a new therapeutic option in patients with ischemic diseases. Many strategies of therapeutic revascularization, based on the administration of growth factors or stem/progenitor cells from diverse sources, have been proposed and are currently tested in patients with peripheral arterial disease or cardiac diseases. This review provides an overview from our current knowledge regarding molecular and cellular mechanisms involved in postischemic revascularization, as well as advances in the clinical application of such strategies of therapeutic revascularization.

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