Cellular senescence in vascular wall mesenchymal stromal cells, a possible contribution to the development of aortic aneurysm

Teti, Gabriella; Chiarini, Francesca; Mazzotti, Eleonora; Ruggeri, Alessandra; Carano, Francesco; Falconi, Mirella

doi:10.1016/j.mad.2021.111515

Cited by 16 publications

(15 citation statements)

References 51 publications

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“…In addition, AAA-ASC showed decreased cell function with mitochondrial kinetic disorder, production of reactive oxygen species (ROS) and decreased mitochondrial membrane potential (96). Similar studies have found that vascular-resident mesenchymal stromal cells (AAA-MSC) and circulating endothelial progenitor cells (EPCs) in patients with AAA have the characteristics of senescent cells and damage of vascular repair ability of MSC (97,98). Besides, another study has found that pretreatment of elderly mice with oral antiaging agents (dasatinib + quercetin) can reduce the abundance of senescent cells in the arterial wall and surrounding tissues, and inhibit the severity of Ang II-induced AAA (99).…”

Section: Evidence and Mechanisms Of Cellular Senescence In Abdominal ...mentioning

confidence: 68%

Cellular senescence and abdominal aortic aneurysm: From pathogenesis to therapeutics

Wang

Hao

Jia

et al. 2022

Front. Cardiovasc. Med.

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As China’s population enters the aging stage, the threat of abdominal aortic aneurysm (AAA) mainly in elderly patients is becoming more and more serious. It is of great clinical significance to study the pathogenesis of AAA and explore potential therapeutic targets. The purpose of this paper is to analyze the pathogenesis of AAA from the perspective of cellular senescence: on the basis of clear evidence of cellular senescence in aneurysm wall, we actively elucidate specific molecular and regulatory pathways, and to explore the targeted drugs related to senescence and senescent cells eliminate measures, eventually improve the health of patients with AAA and prolong the life of human beings.

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Section: Evidence and Mechanisms Of Cellular Senescence In Abdominal ...mentioning

confidence: 68%

Cellular senescence and abdominal aortic aneurysm: From pathogenesis to therapeutics

Wang

Hao

Jia

et al. 2022

Front. Cardiovasc. Med.

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“…Senolytic activity, however, could have an adverse consequence in some situations, as a result of the removal of senescent cells whose presence is essential for maintaining tissue integrity. For instance, human Vascular Smooth Muscle Cells (VSMC) in aneurysmal tissues have been identified to comprise populations of senescent cells [57-62] and their removal could hypothetically result in undesirable aneurysmal rupture with dire physiological consequences. Abdominal Aortic Aneurysm (AAA) is an important health problem with a prevalence of up to 9% in adults over the age of 65 [63-65] , thus the risk to AAA in response to senotherapies merits further investigation.…”

Section: Resultsmentioning

confidence: 99%

Microvesicle-Mediated Tissue Regeneration Mitigates the Effects of Cellular Ageing

Panagiotou

McGuiness

Jaminon

et al. 2022

Preprint

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An ageing global population brings with it a significant burden of age-related morbidities. Recently, a novel intervention strategy to mitigate this burden has emerged, involving the use of Extracellular Vesicles (EV), comprising use of Microvesicles (MV) and Exosomes (Exo). These membranous vesicles are secreted by cells and mediate repair of cellular and tissue damage via paracrine mechanisms, involving interaction of their bioactive cargoes with stem cells. The actions of EV under normative and morbid conditions in the context of ageing remains largely unexplored. We now show that MV, but not Exo, from Pathfinder cells (PC), a putative stem cell regulatory cell type, enhance the repair of Human Dermal Fibroblast (HDF) and Mesenchymal Stem Cell (MSC) co-cultures following both mechanical and genotoxic stress. Critically, this effect was found to be both cellular age and stress-specific. Notably, MV treatment was unable to repair mechanical injury in older co-cultures, but still remained therapeutic following genotoxic stress. These observations were further confirmed in HDF and Vascular Smooth Muscle Cell (VSMC) co-cultures of increasing cellular age. In a model of comorbidity, comprising co-cultures of HDF and highly senescent Abdominal Aortic Aneurysm (AAA) VSMC, MV administration appeared to be senolytic following both mechanical and genotoxic stress, prior to enabling regeneration. To our knowledge, this is the first description of EV-based senolysis. It provides novel insight into understanding the biology of EV and the specific roles they play during tissue repair and ageing. These data will potentiate development of novel cell-free therapeutic interventions capable of attenuating age-associated morbidities and avoiding undesired effects. Ultimately, this might act as a possible intervention strategy to extend human healthspan.

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“…This suggests that CPC-SMPCs and NCSC-SMPCs can differentiate into VSMCs through the SMAD3-dependent TGF-β signaling pathway ( 124 ). ECs differentiation was reduced in patients with AAAs compared with healthy human MSCs, confirming that the aging MSCs impaired its original vascular repair ability, initiating the occurrence and progress of AAAs ( 125 ). Some studies have confirmed that MSCs from calcified and inflammatory aorta have high osteogenic potential and pathological angiogenesis ability under appropriate stimulation ( 126 ).…”

Section: Vascular Wall Stem/progenitor Cells In Vascular Diseasesmentioning

confidence: 88%

Vascular Stem/Progenitor Cells in Vessel Injury and Repair

Jiaping

Cao

et al. 2022

Front. Cardiovasc. Med.

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Vascular repair upon vessel injury is essential for the maintenance of arterial homeostasis and function. Stem/progenitor cells were demonstrated to play a crucial role in regeneration and replenishment of damaged vascular cells during vascular repair. Previous studies revealed that myeloid stem/progenitor cells were the main sources of tissue regeneration after vascular injury. However, accumulating evidences from developing lineage tracing studies indicate that various populations of vessel-resident stem/progenitor cells play specific roles in different process of vessel injury and repair. In response to shear stress, inflammation, or other risk factors-induced vascular injury, these vascular stem/progenitor cells can be activated and consequently differentiate into different types of vascular wall cells to participate in vascular repair. In this review, mechanisms that contribute to stem/progenitor cell differentiation and vascular repair are described. Targeting these mechanisms has potential to improve outcome of diseases that are characterized by vascular injury, such as atherosclerosis, hypertension, restenosis, and aortic aneurysm/dissection. Future studies on potential stem cell-based therapy are also highlighted.

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Cellular senescence in vascular wall mesenchymal stromal cells, a possible contribution to the development of aortic aneurysm

Cited by 16 publications

References 51 publications

Cellular senescence and abdominal aortic aneurysm: From pathogenesis to therapeutics

Cellular senescence and abdominal aortic aneurysm: From pathogenesis to therapeutics

Microvesicle-Mediated Tissue Regeneration Mitigates the Effects of Cellular Ageing

Vascular Stem/Progenitor Cells in Vessel Injury and Repair

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