The Quest for the Adult Cardiac Stem Cell

Noseda, Michela; Paiva, Marta; Schneider, Michael

doi:10.1253/circj.cj-15-0557

Cited by 24 publications

(26 citation statements)

References 92 publications

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“…CPCs have also been identified in the adult mammalian heart using markers including Sca1 and cKit which in small animal studies have demonstrated multi-lineage potency following transplantation to the post-MI myocardium (Ellison et al, 2013; Oh et al, 2003). However, in vitro multi-lineage differentiation of adult CPCs has been difficult to demonstrate especially with regard to differentiation to contracting cardiomyocytes (Noseda et al, 2015), and the regenerative capacity of adult c-kit + CPCs after cardiac injury has been questioned (van Berlo et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

Lineage Reprogramming of Fibroblasts into Proliferative Induced Cardiac Progenitor Cells by Defined Factors

et al. 2016

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Summary Several studies have reported reprogramming of fibroblasts to induced cardiomyocytes; however, reprogramming to proliferative induced cardiac progenitor cells (iCPCs) remains to be accomplished. Here we report that a combination of eleven or five cardiac factors along with canonical Wnt and JAK/STAT signaling reprogrammed adult cardiac, lung and tail-tip fibroblasts into iCPCs. The iCPCs were cardiac mesoderm-restricted progenitors, which could be extensively expanded while maintaining multipotency to differentiate into cardiomyocytes, smooth muscle cells and endothelial cells in vitro. Moreover, iCPCs injected into the cardiac crescent of mouse embryos differentiated into cardiomyocytes. iCPCs transplanted into the post-myocardial infarction mouse heart improved survival and differentiated into cardiomyocytes, smooth muscle cells and endothelial cells. Lineage reprogramming of adult somatic cells into iCPCs provides a scalable cell source for drug discovery, disease modeling, and cardiac regenerative therapy.

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Section: Introductionmentioning

confidence: 99%

Lineage Reprogramming of Fibroblasts into Proliferative Induced Cardiac Progenitor Cells by Defined Factors

et al. 2016

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“…Several studies have reported that mammals generate new mature cells, including cardiomyocytes, throughout their lifetime, although the contribution of different populations to adult cardiac turnover continues to be debated [1]. At difference from other adult tissues, there is no complete characterization of these "progenitor cells", of which SCA1 is the most widely used membrane marker [2,3]. Despite its widespread use as a cardiac progenitor surface marker, SCA1 cardiac cells are a heterogeneous population that includes adult cardiac progenitor cells [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Redox-dependent BMI1 activity drives in vivo adult cardiac progenitor cell differentiation

et al. 2018

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Accumulation of reactive oxygen species (ROS) is associated with several cardiovascular pathologies and with cell cycle exit by neonanatal cardiomyocytes, a key limiting factor in the regenerative capacity of the adult mammalian heart. The polycomb complex component BMI1 is linked to adult progenitors and is an important partner in DNA repair and redox regulation. We found that high BMI1 expression is associated with an adult Sca1 cardiac progenitor sub-population with low ROS levels. In homeostasis, BMI1 repressed cell fate genes, including a cardiogenic differentiation program. Oxidative damage nonetheless modified BMI1 activity in vivo by derepressing canonical target genes in favor of their antioxidant and anticlastogenic functions. This redox-mediated mechanism is not restricted to damage situations, however, and we report ROS-associated differentiation of cardiac progenitors in steady state. These findings demonstrate how redox status influences the cardiac progenitor response, and identify redox-mediated BMI1 regulation with implications in maintenance of cellular identity in vivo.

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“…CSCs have been considered a prospective cell source for myocardial repair following acute myocardial infarction (AMI) due to their self-renewing properties, and their multipotent ability to differentiate into cardiomyocytes and endothelial cells (2,3). CSCs are positive for several stem cell antigens, including stem cell antigen (Sca)-1 and c-Kit (4).…”

Section: Introductionmentioning

confidence: 99%

Resveratrol activates endogenous cardiac stem cells and improves myocardial regeneration following acute myocardial infarction

Lin

Cheng

2017

Molecular Medicine Reports

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Stem cell antigen-1-positive (Sca-1+) cardiac stem cells (CSCs) therapy for myocardial regeneration following acute myocardial infarction (AMI) is limited by insufficient cell viability and a high rate of apoptosis, due to the poor regional microenvironment. Resveratrol, which is a compound extracted from red wine, has been reported to protect myocardial tissue post-AMI by increasing the expression of angiogenic and chemotactic factors. The present study aimed to investigate the effects of resveratrol on Sca-1+ CSCs, and to optimize Sca-1+ CSCs therapy for myocardial regeneration post-AMI. C57/BL6 mice (age, 6 weeks) were divided into two groups, which received intragastric administration of PBS or 2.5 mg/kg.d resveratrol. The endogenous expression of Sca-1+ CSCs in the heart was assessed on day 7. Furthermore, C57/BL6 mice underwent left anterior descending coronary artery ligation for the construction of an AMI model, and received an injection of 1×106 CSCs into the peri-ischemic area (n=8/group). Mice received intragastric administration of PBS or resveratrol (2.5 mg/kg.d) for 4 weeks after cell transplantation. Echocardiography was used to evaluate cardiac function 4 weeks after cell transplantation. Capillary density and cardiomyocyte apoptosis in the peri-ischemic myocardium were assessed by cluster of differentiation 31 immunofluorescent staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, respectively. Western blot analysis was conducted to detect the protein expression levels of vascular endothelial growth factor (VEGF) and stromal cell-derived factor (SDF)-1α in the myocardium. Treatment with resveratrol increased the number of endogenous Sca-1+ CSCs in heart tissue after 7 days (PBS vs. Res, 1.85±0.41/field vs. 3.14±0.26/field, P<0.05). Furthermore, intragastric administration of resveratrol significantly increased left ventricle (LV) function 4 weeks after AMI, as determined by an increase in LV fractional shortening (CSCs vs. Res + CSCs, 28.82±1.58% vs. 31.18±2.02%, P<0.05), reduced LV end-diastolic diameter (CSCs vs. Res + CSCs, 0.37±0.01 mm vs. 0.35±0.02 mm, P<0.05), and reduced LV end-systolic diameter (CSCs vs. Res + CSCs, 0.26±0.01 mm vs. 0.23±0.02 mm, P<0.05). These protective effects were predominantly achieved via an increase in capillary density (CSCs vs. Res + CSCs, 281.02±24.08/field vs. 329.75±36.69/field, P<0.05) and a reduction in cardiomyocyte apoptosis (CSCs vs. Res + CSCs, 1.5±0.54/field vs. 0.83±0.40/field, P<0.05) in peri-ischemic myocardium. Western blot analysis indicated that VEGF and SDF-1α were upregulated in resveratrol-treated myocardium after a 7 day treatment or 4 weeks after AMI (7 days VEGF PBS vs. Res, 0.89±0.07 vs. 1.21±0.02, P<0.05; SDF-1α PBS vs. Res, 0.66±0.04 vs. 1.33±0.04, P<0.05; 4 weeks VEGF CSCs vs. Res + CSCs, 0.54±0.03 vs. 0.93±0.13, P<0.05; SDF-1α CSCs vs. Res + CSCs, 0.53±0.03 vs. 0.93±0.03, P<0.05). Resveratrol activated endogenous CSCs, increased capillary density and decreased cardiomyocyte apoptosis in the peri-ische...

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The Quest for the Adult Cardiac Stem Cell

Cited by 24 publications

References 92 publications

Lineage Reprogramming of Fibroblasts into Proliferative Induced Cardiac Progenitor Cells by Defined Factors

Lineage Reprogramming of Fibroblasts into Proliferative Induced Cardiac Progenitor Cells by Defined Factors

Redox-dependent BMI1 activity drives in vivo adult cardiac progenitor cell differentiation

Resveratrol activates endogenous cardiac stem cells and improves myocardial regeneration following acute myocardial infarction

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