An overview of the myocardial regeneration potential of cardiac c-Kit+ progenitor cells via PI3K and MAPK signaling pathways

2020 ◽  
Vol 16 (3) ◽  
pp. 199-209
Author(s):  
Ezzatollah Fathi ◽  
Behnaz Valipour ◽  
Ilja Vietor ◽  
Raheleh Farahzadi
Keyword(s):  
Progenitor Cells ◽  
Mapk Signaling ◽  
Myocardial Regeneration ◽  
Cardiac Progenitor Cells ◽  
Regeneration Potential ◽  
Innovative Strategy ◽  
Mapk Pathways ◽  
Cardiac Cell Therapy ◽  
Subsequent Activation ◽  
And Migration

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+.

Fabrication of a Nanofibrous Scaffold for the In Vitro Culture of Cardiac Progenitor Cells for Myocardial Regeneration

2013 ◽  
Vol 63 (5) ◽  
pp. 229-239 ◽  
Author(s):  
Rouhollah Mehdinavaz Aghdam ◽  
Saeed Shakhesi ◽  
Siamak Najarian ◽  
Mona Malek Mohammadi ◽  
Seyed Hossein Ahmadi Tafti ◽  
...  
Keyword(s):  
In Vitro Culture ◽  
Progenitor Cells ◽  
Nanofibrous Scaffold ◽  
Myocardial Regeneration ◽  
Cardiac Progenitor Cells

scholarly journals Analysis of Pregnancy-Associated Plasma Protein A Production in Human Adult Cardiac Progenitor Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Piera D’Elia ◽  
Vittoria Ionta ◽  
Isotta Chimenti ◽  
Francesco Angelini ◽  
Fabio Miraldi ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Plasma Protein ◽  
Protein A ◽  
Therapeutic Effects ◽  
Cardiac Progenitor Cells ◽  
Cardiac Cell ◽  
Igf Binding Proteins ◽  
Human Adult ◽  
Igf Binding ◽  
Cardiac Cell Therapy

IGF-binding proteins (IGFBPs) and their proteases regulate IGFs bioavailability in multiple tissues. Pregnancy-associated plasma protein A (PAPP-A) is a protease acting by cleaving IGFBP2, 4, and 5, regulating local bioavailability of IGFs. We have previously shown that IGFs and IGFBPs are produced by human adult cardiac progenitor cells (haCPCs) and that IGF-1 exerts paracrine therapeutic effects in cardiac cell therapy with CPCs. Using immunofluorescence and enzyme immunoassays, we firstly report that PAPP-A is produced and secreted in surprisingly high amounts by haCPCs. In particular, the homodimeric, enzymatically active, PAPP-A is secreted in relevant concentrations in haCPC-conditioned media, while the enzymatically inactive PAPPA/proMBP complex is not detectable in the same media. Furthermore, we show that both homodimeric PAPP-A and proMBP can be detected as cell associated, suggesting that the previously described complex formation at the cell surface does not occur easily, thus positively affecting IGF signalling. Therefore, our results strongly support the importance of PAPP-A for the IGFs/IGFBPs/PAPP-A axis in CPCs biology.

scholarly journals C-Kit Promotes Growth and Migration of Human Cardiac Progenitor Cells via the PI3K-AKT and MEK-ERK Pathways

PLoS ONE ◽  
2015 ◽  
Vol 10 (10) ◽  
pp. e0140798 ◽  
Author(s):  
Bathri N. Vajravelu ◽  
Kyung U. Hong ◽  
Tareq Al-Maqtari ◽  
Pengxiao Cao ◽  
Matthew C. L. Keith ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Cardiac Progenitor Cells ◽  
And Migration

Abstract 1018: Cardiac Progenitor Cells and Biotinylated IGF-1 Nanofibers Improve Endogenous and Exogenous Myocardial Regeneration after Infarction

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Yu Misao ◽  
Michael E Davis ◽  
Vincent E Segers ◽  
Marcello Rota ◽  
Grazia Esposito ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Combined Treatment ◽  
Volume Ratio ◽  
Experimental Period ◽  
Border Zone ◽  
Myocardial Regeneration ◽  
Prolonged Release ◽  
Cardiac Progenitor Cells ◽  
Receptor System ◽  
Chamber Volume

Cardiac progenitor cells (CPCs) possess the IGF-1-IGF-1 receptor system which promotes cell survival, growth and differentiation. Therefore, we tested whether the local injection of CPCs together with the prolonged release of IGF-1 by self-assembling peptides enhanced myocardial regeneration after infarction. The possibility was raised that this strategy may improve cardiac repair by potentiating the regenerative response of the delivered and resident CPCs. Myocardial infarction was induced in rats and after the injection of 100,000 clonogenic immunocompatible EGFP-positive-CPCs in the border zone, biotinylated IGF-1 nanofibers were delivered to the same region. Four groups of animals were used for comparison: infarcted hearts injected with peptide only, infarcted hearts injected with CPCs only, untreated infarcted hearts and sham operated hearts. All animals received BrdU throughout the 1 month experimental period for the recognition of newly formed cells. Infarct size, ~60%, was comparable in the 4 groups. Although all treated-infarcted hearts showed a reduction in chamber volume and an increase in wall-thickness-to-chamber volume ratio and LV mass-to-chamber volume ratio, the combined treatment had the most positive effect. Similarly, LVEDP, LVDP, and dP/dt improved predominantly in infarcted hearts exposed to CPCs and IGF-1 which possessed a larger number of regenerated myocytes. The newly formed BrdU-positive myocytes consisted of EGFP-positive and EGFP-negative cells. The former category corresponded to the progeny of the injected CPCs and the latter was the product of differentiation of resident CPCs. The regenerated myocytes showed a high degree of differentiation; 20% of myocytes had a volume 2,000 –10,000 μm 3 . This level of maturation was not observed in infarcted hearts treated only with CPCs or IGF1 releasing peptides. Also, administration of CPCs and IGF-1 led to the formation of numerous resistance arterioles and capillary structures within the regenerated myocardium. Thus, the combination of CPCs and IGF-1 biotinylated nanofibers results in an unprecedented degree of myocardial recovery of structure and function after infarction. Importantly, the regenerated myocytes acquire the differentiated adult phenotype.

Abstract 21: Ploidy Alteration of Murine Cardiac Progenitor Cells in Response to Infarction Injury

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Kathleen M Broughton ◽  
Bingyan J Wang ◽  
Taeyong Kim ◽  
Sadia Mohsin ◽  
Dieter Kubli ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Biological Properties ◽  
Border Zone ◽  
Myocardial Regeneration ◽  
Mouse Strains ◽  
Cardiac Progenitor Cells ◽  
Regenerative Capacity ◽  
Clonal Lines ◽  
And Gender ◽  
Species Specific

Introduction: Discovery of endogenous cardiac progenitor cells (CPC) prompted intense research efforts in multiple experimental animal models and clinical trials for heart failure treatment. Our lab identified a fundamental difference in ploidy content between rodent (rat, mouse) CPCs possessing mononuclear tetraploid (4n) chromosome content versus large mammal (human, swine) CPCs with mononuclear diploid (2n) content. Ploidy differences raise provocative questions regarding translational applicability of myocardial regeneration in rodents as polyplodization often correlates with enhanced regenerative potential. Hypothesis: Mononuclear chromatin duplication in CPCs improves regenerative capacity of the heart through higher stress resistance and overriding senescence cell-cycle arrest. Methods and Results: Ploidy of cultured CPCs is consistent and stable ploidy content over increased passages with samples from eight humans, two swine strains, six mouse strains, and seven rat clonal lines as determined by karyotype, confocal microscope and flow cytometry analyses. In situ ploidy analysis of CPCs reveals diploid content in human tissue and a mixture of mononuclear diploid and tetraploid nuclei in mouse, confirmed using freshly isolated Lin- c-kit+ CPCs. Tetraploid nuclear phenotype of murine CPCs is markedly different from predominantly diploid (2n) murine c-kit+ cells located in other tissues such as intestine and bone marrow. Higher ploidy content concurrent with expansion of the CPC pool are evident in the border zone at seven days post-infarction in adult FVB mice compared to age and gender matched non-injured hearts. Conclusion: Tetraploid c-kit+ cells found within the rodent heart may contribute to species-specific characteristics of stem cells and myocardial regenerative capacity. Future studies will focus upon the biological properties of diploid versus tetraploid CPCs and advantages of polyploid content for mediating myocardial regeneration.

Abstract 710: Notch1 Receptor Enhances Myocyte Differentiation of Cardiac Progenitor Cells and Myocardial Regeneration After Infarction

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Alessandro Boni ◽  
Angelo Nascimbene ◽  
Robert Siggins ◽  
Konrad Urbanek ◽  
Katsuya Amano ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Notch Pathway ◽  
Border Zone ◽  
Myocardial Regeneration ◽  
Mouse Heart ◽  
Cardiac Progenitor Cells ◽  
Notch 1 ◽  
Secretase Inhibitor

Cardiac progenitor cells (CPCs) have been identified in the adult heart. However, the molecular mechanisms involved in the commitment of CPCs to the myocyte lineage remain to be determined. Notch-1 is a transmembrane receptor activated by the DSL family of ligands which include Jagged1 and Delta-4. Upon ligand binding, the activated receptor undergoes cleavage by γ-secretase, and its intracellular portion (Notch intracellular domain, NICD) is released, translocates to the nucleus and exerts its function as a transcriptional regulator. The objective of this study was to determine whether the components of the Notch pathway are present in the CPCs of the adult mammalian heart and whether activation of the Notch-1 receptor promotes the differentiation of CPCs into myocytes. For this purpose, c-kit-positive CPCs were isolated from the mouse heart and analyzed by FACS and immunocytochemistry. Notch-1 receptor was detected in ~50% of c-kit-positive CPCs. CPCs were then plated on culture dishes coated with immobilized Jagged1 or Delta-4 and maintained in low-serum medium. Additional groups of cells were similarly exposed to the ligands but were also treated with γ-secretase inhibitor. After 5 days in culture, the number of CPCs was markedly lower in the presence of the Notch ligands and significantly higher in the presence of the γ-secretase inhibitor. After 8 days in culture, cells became confluent and did not express any longer c-kit. With respect to cells treated with the γ-secretase inhibitor, exposure to Jagged1 and Delta-4 resulted respectively in a 10-fold and 20-fold increase in the fraction of CPCs positive for Nkx2.5. These findings were consistent with a positive effect of Notch on CPC differentiation and Nkx2.5 upregulation. To establish whether Notch influenced cardiomyogenesis in vivo, infarcted mice were treated for 11 days with the γ-secretase inhibitor. The regenerative response of the infarcted heart, defined by the percentage of BrdU-positive myocytes distributed in the border zone, was 50% lower in animals that received the γ-secretase inhibitor. Thus, Notch1 modulates CPC differentiation in vitro and myocardial regeneration in vivo after infarction.

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