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 ◽  
...  
2020 ◽  
Vol 16 (3) ◽  
pp. 199-209
Author(s):  
Ezzatollah Fathi ◽  
Behnaz Valipour ◽  
Ilja Vietor ◽  
Raheleh Farahzadi

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+.


2020 ◽  
Vol 12 (5) ◽  
pp. 2614-2624 ◽  
Author(s):  
Chuanchuan Li ◽  
Yan Zhang ◽  
Yuan Tang ◽  
Jinwen Xiao ◽  
Feng Gao ◽  
...  

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Guillermo Albericio ◽  
Susana Aguilar ◽  
Jose Luis Torán ◽  
Rosa Yañez ◽  
Juan Antonio López ◽  
...  

AbstractClinical trials evaluating cardiac progenitor cells (CPC) demonstrated feasibility and safety, but no clear functional benefits. Therefore a deeper understanding of CPC biology is warranted to inform strategies capable to enhance their therapeutic potential. Here we have defined, using a label-free proteomic approach, the differential cytoplasmic and nuclear compartments of human CPC (hCPC). Global analysis of cytoplasmic repertoire in hCPC suggested an important hypoxia response capacity and active collagen metabolism. In addition, comparative analysis of the nuclear protein compartment identified a significant regulation of a small number of proteins in hCPC versus human mesenchymal stem cells (hMSC). Two proteins significantly upregulated in the hCPC nuclear compartment, IL1A and IMP3, showed also a parallel increase in mRNA expression in hCPC versus hMSC, and were studied further. IL1A, subjected to an important post-transcriptional regulation, was demonstrated to act as a dual-function cytokine with a plausible role in apoptosis regulation. The knockdown of the mRNA binding protein (IMP3) did not negatively impact hCPC viability, but reduced their proliferation and migration capacity. Analysis of a panel of putative candidate genes identified HMGA2 and PTPRF as IMP3 targets in hCPC. Therefore, they are potentially involved in hCPC proliferation/migration regulation.


2015 ◽  
Vol 179 ◽  
pp. 393-396 ◽  
Author(s):  
Wenya Ma ◽  
Liang Zhao ◽  
Kun Yin ◽  
Dan Feng ◽  
Fan Yang ◽  
...  

2010 ◽  
Vol 316 (20) ◽  
pp. 3435-3442 ◽  
Author(s):  
Yangxin Li ◽  
Jiangbo Qu ◽  
Harnath Shelat ◽  
Song Gao ◽  
Michael Wassler ◽  
...  

2007 ◽  
Vol 55 (S 1) ◽  
Author(s):  
M Arnold ◽  
V Kufer ◽  
A Schütz ◽  
B Reiter ◽  
M Fittkau ◽  
...  

2012 ◽  
Vol 7 (1) ◽  
pp. 14
Author(s):  
Christian Homsy ◽  

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.


Diabetologia ◽  
2021 ◽  
Author(s):  
Nima Purvis ◽  
Sweta Kumari ◽  
Dhananjie Chandrasekera ◽  
Jayanthi Bellae Papannarao ◽  
Sophie Gandhi ◽  
...  

2021 ◽  
Vol 22 (3) ◽  
pp. 1390
Author(s):  
Julia Mester-Tonczar ◽  
Patrick Einzinger ◽  
Johannes Winkler ◽  
Nina Kastner ◽  
Andreas Spannbauer ◽  
...  

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.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii295-iii295
Author(s):  
Mikaela Nevin ◽  
Janine Gallego ◽  
Xiaohua Song ◽  
Qiang Jiang ◽  
Alan Underhill ◽  
...  

Abstract BACKGROUND The identification of H3.3/H3.1K27M in most DIPG has changed our understanding of this disease. H3K27M mutations usually demonstrate global loss of H3K27 trimethylation (me3) with gain of H3K27 acetylation (ac). Single cell RNAseq has identified the putative cell of origin as oligodendroglial progenitor cells (OPC). The distalless gene family is necessary for the differentiation and tangential migration of committed neural progenitors to become GABAergic interneurons. Dlx1/Dlx2 double knockout (DKO) cells from the ganglionic eminences (GE) transplanted into a wild-type environment become oligodendrocytes. RESULTS We identified DLX2 occupancy of early (Olig2, Nkx2.2) and late (Myt1, Plp1) genes required for OPC differentiation in vivo and confirmed direct DLX2 protein-promoter DNA binding in vitro. Co-expression of Dlx2 with target sequences reduced reporter gene expression in vitro. There was increased expression of OLIG2, NKX2.2 and PLP-1 expression in vivo, consistent with de-repression in the absence of Dlx1/Dlx2 function. Transient over-expression of a Dlx2-GFP construct into murine DIPG cells from a GEMM that develops DIPG resulted in significant increases in expression of Gad isoforms with concomitant decreases in Olig2 and Nkx2.2. Dlx2-transfected mDIPG cells also demonstrated reduced migration, invasion and colony formation in vitro. Of significance, there was global restoration of H3K27me3 with corresponding loss of H3K27ac expression in transfected cells compared to controls. CONCLUSIONS DLX2 promotes GABAergic differentiation and migration while concomitantly repressing OPC differentiation in vivo. Developmental reprogramming of mDIPG cells by DLX2 demonstrates the potential role for directed differentiation strategies towards improving patient outcomes for this devastating pediatric cancer.


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