scholarly journals Comparative proteomic analysis of nuclear and cytoplasmic compartments in human cardiac progenitor cells

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Guillermo Albericio ◽  
Susana Aguilar ◽  
Jose Luis Torán ◽  
Rosa Yañez ◽  
Juan Antonio López ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Therapeutic Potential ◽  
Global Analysis ◽  
Human Mesenchymal Stem Cells ◽  
Dual Function ◽  
Cardiac Progenitor Cells ◽  
Label Free ◽  
Proteomic Approach ◽  
And Migration ◽  
Migration Capacity

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.

scholarly journals Comparative Proteomic Analysis of Nuclear and Cytoplasmic Compartments in Human Cardiac Progenitor Cells. Functional Evaluation of IL1A and IMP3

2021 ◽  
Author(s):  
Guillermo Albericio ◽  
Susana Aguilar ◽  
Jose Luis Torán ◽  
Rosa Yañez ◽  
Juan Antonio López ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Therapeutic Potential ◽  
Global Analysis ◽  
Human Mesenchymal Stem Cells ◽  
Dual Function ◽  
Cardiac Progenitor Cells ◽  
Functional Evaluation ◽  
Label Free ◽  
Proteomic Approach ◽  
Migration Capacity

Abstract Clinical 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.

scholarly journals After the Storm: An Objective Appraisal of the Efficacy of c-kit+ Cardiac Progenitor Cells in Preclinical Models of Heart Disease

2020 ◽  
Author(s):  
Roberto Bolli ◽  
Xian-Liang Tang ◽  
Yiru Guo ◽  
Qianhong Li
Keyword(s):  
Progenitor Cells ◽  
Ischemic Cardiomyopathy ◽  
Therapeutic Potential ◽  
Clinical Work ◽  
Good Faith ◽  
Cardiac Progenitor Cells ◽  
Review Of The Literature ◽  
Preclinical Models ◽  
Beneficial Effects ◽  
Retraction Notice

The falsification of data related to c-kit+ cardiac progenitor cells (CPCs) by a Harvard laboratory has been a veritable tragedy. Does this fraud mean that CPCs are not beneficial in models of ischemic cardiomyopathy? At least 50 studies from 26 laboratories independent of the Harvard group have reported beneficial effects of CPCs in mice, rats, pigs, and cats. The mechanism of action remains unclear. Our group has shown that CPCs do not engraft in the diseased heart, do not differentiate into new cardiac myocytes, do not regenerate dead myocardium, and thus work via paracrine mechanisms. A casualty of the misconduct at Harvard has been the SCIPIO trial, a collaboration between the Harvard group and the group in Louisville. The retraction of the SCIPIO paper was caused exclusively by issues with data generated at Harvard, not those generated in Louisville. In the retraction notice, the Lancet editors stated: “Although we do not have any reservations about the clinical work in Louisville that used the preparations from Anversa's laboratory in good faith, the lack of reliability regarding the laboratory work at Harvard means that we are now retracting this paper.” We must be careful not to dismiss all work on CPCs because of one laboratory’s misconduct. An unbiased review of the literature supports the therapeutic potential of CPCs for heart failure at the preclinical level.

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

scholarly journals Human iPS Cells Derived Skeletal Muscle Progenitor Cells Promote Myoangiogenesis and Restore Dystrophin in Duchenne Muscular Dystrophic Mice

2020 ◽  
Author(s):  
Wanling Xuan ◽  
Mahmood Khan ◽  
Muhammad Ashraf
Keyword(s):  
Progenitor Cells ◽  
Inflammatory Cells ◽  
Tibialis Muscle ◽  
Cellular Source ◽  
Muscle Necrosis ◽  
Muscle Progenitor Cells ◽  
And Migration ◽  
Induced Pluripotent ◽  
Migration Capacity ◽  
Muscle Gene

AbstractBackground and ObjectiveDuchenne muscular dystrophy (DMD) is caused by mutations of the gene that encodes the protein dystrophin. Loss of dystrophin leads to severe and progressive muscle-wasting in both skeletal and heart muscles. Human induced pluripotent stem cells (hiPSCs) and their derivatives offer important opportunities to treat a number of diseases. Here, we investigated whether givinostat, a histone deacetylase inhibitor (HDACi), could reprogram hiPSCs into muscle progenitor cells (MPC) for DMD treatment.Methods and ResultsMPC generated by CHIR99021 and givinostat (Givi) small molecules from multiple hiPSCs expressed myogenic makers (Pax7, desmin) and were differentiated into myotubes expressing MF20 upon culture in specific differentiation medium. These MPC exhibited superior proliferation and migration capacity determined by CCK-8, colony and migration assays compared to control-MPC generated by CHIR99021 and fibroblast growth factor (FGF). Upon transplantation in hind limb of Mdx/SCID mice with cardiotoxin (CTX) induced injury, these MPC showed higher engraftment and restoration of dystrophin than treatment with control-MPC and human myoblasts. In addition, treated muscle with these MPC showed significantly limited infiltration of inflammatory cells and reduced muscle necrosis and fibrosis. A number of these cells were engrafted under basal lamina expressing Pax7, which were capable of generating new muscle fibers after additional injury. Extracellular vesicles released from these cells promoted angiogenesis after reinjury.ConclusionWe successfully generated integration free MPC from multiple hiPS cell lines using CHIR99021 and Givi. Givinostat induced MPC showed marked and impressive regenerative capabilities and restored dystrophin in injured tibialis muscle compared to control MPC. Additionally, MPC generated by Givi also seeded the stem cell pool in the treated muscle. It is concluded that hiPSCs pharmacologically reprogrammed into MPC with a small molecule, Givi with anti-oxidative, anti-inflammatory and muscle gene promoting properties might be an effective cellular source for treatment of muscle injury and restoration of dystrophin in DMD.

scholarly journals Short Communication: The Effect of Different Concentrations of Methylprednisolone on Survival, Proliferation and Migration of Neural Stem/Progenitor Cells

2021 ◽  
Author(s):  
Zohreh Bagheri ◽  
◽  
Fatemeh Shamsi ◽  
Zahra Zeraatpisheh ◽  
Mahin Salman Nejad ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Progenitor Cells ◽  
Mtt Assay ◽  
Short Communication ◽  
Neural Stem Progenitor Cells ◽  
And Migration ◽  
Migration Capacity ◽  
Neurosphere Assay ◽  
Different Doses ◽  
Proliferation And Migration

Introduction: To address the question whether combination of methylprednisolone (MP) as an anti-inflammatory drug used in neurodegenerative diseases and neural stem/progenitor cells (NS/PCs) is safe, the present study was designed. Methods: Embryonic rat NS/PCs were exposed to different doses of MP and survival by MTT assay, proliferation by analyzing the number and diameter of neurospheres and the migration of the cells by neurosphere assay were evaluated. Results: The viability of NS/PCs reduced following exposure to 10, 15 and 20 µg/ml of MP. In addition, although the number of neurospheres didn’t change, exposure to different doses of MP resulted in formation of smaller neurospheres. Despite these undesirable effects, the highest concentration of MP (20 μg/ml) increased the migration capacity of the NS/PCs. Conclusion: The combination of MP and NS/PCs is not recommended due to the adverse effects of MP on survival and proliferation of NS/PCs.

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+.

scholarly journals LncRNA CRNDE modulates cardiac progenitor cells’ proliferation and migration via the miR-181a/LYRM1 axis in hypoxia

2020 ◽  
Vol 12 (5) ◽  
pp. 2614-2624 ◽  
Author(s):  
Chuanchuan Li ◽  
Yan Zhang ◽  
Yuan Tang ◽  
Jinwen Xiao ◽  
Feng Gao ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Cardiac Progenitor Cells ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals Epicardial Transplantation of Cardiac Progenitor Cells Based Cells Sheets is More Promising Method for Stimulation of Myocardial Regeneration, Than Conventional Cell Injections

Kardiologiia ◽  
2019 ◽  
Vol 59 (5) ◽  
pp. 53-60 ◽  
Author(s):  
K. V. Dergilev ◽  
Z. I. Tsokolayeva ◽  
I. B. Beloglazova ◽  
E. I. Ratner ◽  
E. V. Parfyonova
Keyword(s):  
Progenitor Cells ◽  
Cardiac Remodeling ◽  
Progenitor Cell ◽  
Therapeutic Potential ◽  
Heart Diseases ◽  
Cardiac Progenitor Cells ◽  
Cell Sheets ◽  
Intramyocardial Delivery ◽  
Conventional Cell ◽  
Stimulation Of

Today, transplantation of stem / progenitor cells is a promising approach for the treatment of heart diseases. The therapeutic potential of transplanted cells directly depends on the method of delivery to the myocardium, which determines their regenerative properties. It is important for the development of effective methods of cell therapy. In this paper, we performed a comparative study of efficacy of cardiac progenitor cell (CPC) transplantation by intramyocardial needle injections and by tissue engineering constructs (TEC) – “cell sheets” consisting of cells and their extracellular matrix. It has been shown, that transplantation of TEC in comparison with the intramyocardial delivery provides more extensive distribution and retains more proliferating cellular elements in the damaged myocardium, attenuates the negative cardiac remodeling of the left ventricle and promotes its vascularization.   

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