Cardiac stem cell aging and heart failure

Cesselli, Daniela; Aleksova, Aneta; Mazzega, Elisa; Caragnano, Angela; Beltrami, Antonio Paolo

doi:10.1016/j.phrs.2017.01.013

Cited by 12 publications

(11 citation statements)

References 112 publications

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“…Investigators have demonstrated that the number of the left ventricle cardiomyocytes progressively declines with aging 5 . Several studies have reported that undifferentiated primitive cells reside in mammalian hearts and protect them against heart failure 1,6,7 . Furthermore, senescent and dysfunctional resident human cardiac progenitor cells (hCPCs) accumulate as a consequence of cardiac pathology [8][9][10][11][12] and lead to premature cardiac aging and heart failure 13 .…”

Section: Introductionmentioning

confidence: 99%

Pharmacological inhibition of mTOR attenuates replicative cell senescence and improves cellular function via regulating the STAT3-PIM1 axis in human cardiac progenitor cells

et al. 2020

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The mammalian target of rapamycin (mTOR) signaling pathway efficiently regulates the energy state of cells and maintains tissue homeostasis. Dysregulation of the mTOR pathway has been implicated in several human diseases. Rapamycin is a specific inhibitor of mTOR and pharmacological inhibition of mTOR with rapamycin promote cardiac cell generation from the differentiation of mouse and human embryonic stem cells. These studies strongly implicate a role of sustained mTOR activity in the differentiating functions of embryonic stem cells; however, they do not directly address the required effect for sustained mTOR activity in human cardiac progenitor cells. In the present study, we evaluated the effect of mTOR inhibition by rapamycin on the cellular function of human cardiac progenitor cells and discovered that treatment with rapamycin markedly attenuated replicative cell senescence in human cardiac progenitor cells (hCPCs) and promoted their cellular functions. Furthermore, rapamycin not only inhibited mTOR signaling but also influenced signaling pathways, including STAT3 and PIM1, in hCPCs. Therefore, these data reveal a crucial function for rapamycin in senescent hCPCs and provide clinical strategies based on chronic mTOR activity.

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Section: Introductionmentioning

confidence: 99%

Pharmacological inhibition of mTOR attenuates replicative cell senescence and improves cellular function via regulating the STAT3-PIM1 axis in human cardiac progenitor cells

et al. 2020

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“…Previous research has explored key molecular pathways that are often disrupted when tissue and stem cell senescence and degradation, and experimental evidence supports these pathways themselves can reverse the aging phenotype. However, the mechanisms related to the rejuvenation of tissues have yet to be fully elucidated [24].…”

Section: Impact Of Stem Cell Senescence In Aging and Diseasesmentioning

confidence: 99%

“…We are still far from a definite quantitative measure of cardiac turnover; however, it has finally been accepted that heart muscle cells can be regenerated after birth [24] [79] [80]. Nonetheless, mature cardiomyocytes are withdrawn from the cell cycle soon after birth [81] [82] [83].…”

Section: Cardiac Rejuvenationmentioning

confidence: 99%

“…Patients with severe obstructive cardiac disease caused by the narrowing of atherosclerotic plaques present tissue retention and a reduction in the functionality of circulating vascular stem/progenitor cells to repair tissue damage [84]. This has led a number of researchers to use stem cell transplantation as a means to regenerate tissue heart in a process referred to as heart rejuvenation [24].…”

Section: Cardiac Rejuvenationmentioning

confidence: 99%

“…[89]. Researchers have also investigated cell therapies involving the administration of young, healthy stem cells to a diseased heart to provide protection from cardiomyocyte senescence and promote cardiac repair [24] [90] [91]. They also investigated the ex vivo rejuvenation of reparative cells through the in vitro pharmacological pretreatment of stem cells isolated from old diseased animals followed by in vivo delivery.…”

Section: Cardiac Rejuvenationmentioning

confidence: 99%

See 2 more Smart Citations

Therapeutics of Stem Cell Treatment in Anti-Aging and Rejuvenation

Yeh¹,

Chan²

2018

SCD

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Aging populations are increasing the incidence of age-related diseases, resulting in problems at the individual and socioeconomic level. The need for effective strategies in regenerative medicine for the elderly is more important than ever. Previous studies have shown that the number and function of stem cells decline with age, thereby undermining endogenous repair processes. It has also been suggested that the aging-induced deterioration of stem cell function may play a key role in the pathophysiology of various aging-related diseases. Recent advances in our understanding of tissue regeneration and the development of methods aimed at inducing and differentiating pluripotent stem cells for cell replacement therapy which provides exciting opportunities for the treatment of degenerative diseases, such as those related to senility. In this review article, we examine several mechanisms that are believed to contribute to the aging-related dysfunction of stem cells associated with diseases of the immune system, cardiac tissue, neuronal system, articular cartilage, and skeletal muscle. We also discuss factors that affect the therapeutic potential of adult stem/progenitor cells as well as current trends in the treatment of these conditions using regenerative medicine.

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